Immunology

The reported link between early life exposure to acetaminophen and the development of asthma in children is “weak” and “overstated” based on currently available evidence, according to a report published by the Archives of Disease in Childhood.

In a review of currently available data culled from Embase and PubMed databases, 1,192 relevant studies conducted between 1967 and 2013 were analyzed, of which 11 were included for analysis. Of these 11 studies, 5 found “increased odds” that exposure to acetaminophen during the first trimester of pregnancy could lead to development of asthma (pooled odds ratio, 1.39); however, there was a high degree of between-study heterogeneity among the trials (I² = 64.2%, P = .03), reported Dr. M. Cheelo of the University of Melbourne, and associates.

Of those five, only two studies examined the effects of acetaminophen exposure during the second trimester, but attained widely disparate results: Study one reported an OR of 1.06, while the other reported an OR of 2.15, with I² = 80%. Two studies also tested acetaminophen exposure during the third trimester and found a “weak association,” with a pooled OR of 1.17. Three studies look at acetaminophen exposure through an entire pregnancy, but all had “significant heterogeneity” in their findings (OR = 1.65, 1.22, and 0.74; I² = 89%). Only one study that was examined adjusted for respiratory tract infections during pregnancy, but according to the authors, “all studies that adjusted for early life respiratory tract infections found a reduction in the association between [acetaminophen] exposure and subsequent childhood asthma” (Arch. Dis. Child. 2014 [doi:10.1136/archdischild-2012-303043]).

The other 6 of the 11 total studies examined acetaminophen exposure over the first 2 years of life. Three of these studies found a “weak positive association,” as did four studies directly comparing children with and without acetaminophen exposure. All but one study adjusted results for respiratory tract infections during pregnancy, which caused a “moderate attenuation of the association between frequency of [acetaminophen] intake and childhood asthma.” Consequently, investigators concluded that “evidence of an association between early life [acetaminophen] and asthma is often overstated, and there is currently insufficient evidence to support changing guidelines in the use of this medicine.”

The authors reported no relevant financial conflicts of interest.

The reported link between early life exposure to acetaminophen and the development of asthma in children is “weak” and “overstated” based on currently available evidence, according to a report published by the Archives of Disease in Childhood.

In a review of currently available data culled from Embase and PubMed databases, 1,192 relevant studies conducted between 1967 and 2013 were analyzed, of which 11 were included for analysis. Of these 11 studies, 5 found “increased odds” that exposure to acetaminophen during the first trimester of pregnancy could lead to development of asthma (pooled odds ratio, 1.39); however, there was a high degree of between-study heterogeneity among the trials (I² = 64.2%, P = .03), reported Dr. M. Cheelo of the University of Melbourne, and associates.

Of those five, only two studies examined the effects of acetaminophen exposure during the second trimester, but attained widely disparate results: Study one reported an OR of 1.06, while the other reported an OR of 2.15, with I² = 80%. Two studies also tested acetaminophen exposure during the third trimester and found a “weak association,” with a pooled OR of 1.17. Three studies look at acetaminophen exposure through an entire pregnancy, but all had “significant heterogeneity” in their findings (OR = 1.65, 1.22, and 0.74; I² = 89%). Only one study that was examined adjusted for respiratory tract infections during pregnancy, but according to the authors, “all studies that adjusted for early life respiratory tract infections found a reduction in the association between [acetaminophen] exposure and subsequent childhood asthma” (Arch. Dis. Child. 2014 [doi:10.1136/archdischild-2012-303043]).

The other 6 of the 11 total studies examined acetaminophen exposure over the first 2 years of life. Three of these studies found a “weak positive association,” as did four studies directly comparing children with and without acetaminophen exposure. All but one study adjusted results for respiratory tract infections during pregnancy, which caused a “moderate attenuation of the association between frequency of [acetaminophen] intake and childhood asthma.” Consequently, investigators concluded that “evidence of an association between early life [acetaminophen] and asthma is often overstated, and there is currently insufficient evidence to support changing guidelines in the use of this medicine.”

The authors reported no relevant financial conflicts of interest.

The reported link between early life exposure to acetaminophen and the development of asthma in children is “weak” and “overstated” based on currently available evidence, according to a report published by the Archives of Disease in Childhood.

In a review of currently available data culled from Embase and PubMed databases, 1,192 relevant studies conducted between 1967 and 2013 were analyzed, of which 11 were included for analysis. Of these 11 studies, 5 found “increased odds” that exposure to acetaminophen during the first trimester of pregnancy could lead to development of asthma (pooled odds ratio, 1.39); however, there was a high degree of between-study heterogeneity among the trials (I² = 64.2%, P = .03), reported Dr. M. Cheelo of the University of Melbourne, and associates.

Of those five, only two studies examined the effects of acetaminophen exposure during the second trimester, but attained widely disparate results: Study one reported an OR of 1.06, while the other reported an OR of 2.15, with I² = 80%. Two studies also tested acetaminophen exposure during the third trimester and found a “weak association,” with a pooled OR of 1.17. Three studies look at acetaminophen exposure through an entire pregnancy, but all had “significant heterogeneity” in their findings (OR = 1.65, 1.22, and 0.74; I² = 89%). Only one study that was examined adjusted for respiratory tract infections during pregnancy, but according to the authors, “all studies that adjusted for early life respiratory tract infections found a reduction in the association between [acetaminophen] exposure and subsequent childhood asthma” (Arch. Dis. Child. 2014 [doi:10.1136/archdischild-2012-303043]).

The other 6 of the 11 total studies examined acetaminophen exposure over the first 2 years of life. Three of these studies found a “weak positive association,” as did four studies directly comparing children with and without acetaminophen exposure. All but one study adjusted results for respiratory tract infections during pregnancy, which caused a “moderate attenuation of the association between frequency of [acetaminophen] intake and childhood asthma.” Consequently, investigators concluded that “evidence of an association between early life [acetaminophen] and asthma is often overstated, and there is currently insufficient evidence to support changing guidelines in the use of this medicine.”

The authors reported no relevant financial conflicts of interest.

The Food and Drug Administration has approved the 40-mcg dose of QNASL for use in the treatment of nasal symptoms associated with allergic rhinitis in children aged 4-11 years, making it the first waterless nasal allergy spray approved for use in children as young as 4 years old.

“Through the availability of QNASL [beclomethasone dipropionate] 40 mcg, we are aiming to aid children and their caregivers in better managing the burdensome symptoms associated with nasal allergies,” said Dr. Tushar Shah, senior vice president of Teva Global Respiratory Research and Development.

The FDA approved beclomethasone dipropionate 40 mcg based on data from three double-blind, placebo-controlled studies of children aged 4-11 years. In those studies, once-daily beclomethasone dipropionate 40 mcg alleviated allergy symptoms in children with both seasonal and perennial allergic rhinitis with a minimum of adverse effects. The most common side effects were nosebleed and ulcers, which was “consistent with those seen in previous clinical studies of QNASL Nasal Aerosol,” according to a statement from the manufacturer.

QNASL40 mcg is expected to become available in February 2015.

The Food and Drug Administration has approved the 40-mcg dose of QNASL for use in the treatment of nasal symptoms associated with allergic rhinitis in children aged 4-11 years, making it the first waterless nasal allergy spray approved for use in children as young as 4 years old.

“Through the availability of QNASL [beclomethasone dipropionate] 40 mcg, we are aiming to aid children and their caregivers in better managing the burdensome symptoms associated with nasal allergies,” said Dr. Tushar Shah, senior vice president of Teva Global Respiratory Research and Development.

The FDA approved beclomethasone dipropionate 40 mcg based on data from three double-blind, placebo-controlled studies of children aged 4-11 years. In those studies, once-daily beclomethasone dipropionate 40 mcg alleviated allergy symptoms in children with both seasonal and perennial allergic rhinitis with a minimum of adverse effects. The most common side effects were nosebleed and ulcers, which was “consistent with those seen in previous clinical studies of QNASL Nasal Aerosol,” according to a statement from the manufacturer.

QNASL40 mcg is expected to become available in February 2015.

The Food and Drug Administration has approved the 40-mcg dose of QNASL for use in the treatment of nasal symptoms associated with allergic rhinitis in children aged 4-11 years, making it the first waterless nasal allergy spray approved for use in children as young as 4 years old.

“Through the availability of QNASL [beclomethasone dipropionate] 40 mcg, we are aiming to aid children and their caregivers in better managing the burdensome symptoms associated with nasal allergies,” said Dr. Tushar Shah, senior vice president of Teva Global Respiratory Research and Development.

The FDA approved beclomethasone dipropionate 40 mcg based on data from three double-blind, placebo-controlled studies of children aged 4-11 years. In those studies, once-daily beclomethasone dipropionate 40 mcg alleviated allergy symptoms in children with both seasonal and perennial allergic rhinitis with a minimum of adverse effects. The most common side effects were nosebleed and ulcers, which was “consistent with those seen in previous clinical studies of QNASL Nasal Aerosol,” according to a statement from the manufacturer.

QNASL40 mcg is expected to become available in February 2015.

The Food and Drug Administration has approved the 40-mcg dose of QNASL for use in the treatment of nasal symptoms associated with allergic rhinitis in children aged 4-11 years, making it the first waterless nasal allergy spray approved for use in children as young as 4 years old.

“Through the availability of QNASL [beclomethasone dipropionate] 40 mcg, we are aiming to aid children and their caregivers in better managing the burdensome symptoms associated with nasal allergies,” said Dr. Tushar Shah, senior vice president of Teva Global Respiratory Research and Development.

The FDA approved beclomethasone dipropionate 40 mcg based on data from three double-blind, placebo-controlled studies of children aged 4-11 years. In those studies, once-daily beclomethasone dipropionate 40 mcg alleviated allergy symptoms in children with both seasonal and perennial allergic rhinitis with a minimum of adverse effects. The most common side effects were nosebleed and ulcers, which was “consistent with those seen in previous clinical studies of QNASL Nasal Aerosol,” according to a statement from the manufacturer.

QNASL40 mcg is expected to become available in February 2015.

[email protected]

The Food and Drug Administration has approved the 40-mcg dose of QNASL for use in the treatment of nasal symptoms associated with allergic rhinitis in children aged 4-11 years, making it the first waterless nasal allergy spray approved for use in children as young as 4 years old.

“Through the availability of QNASL [beclomethasone dipropionate] 40 mcg, we are aiming to aid children and their caregivers in better managing the burdensome symptoms associated with nasal allergies,” said Dr. Tushar Shah, senior vice president of Teva Global Respiratory Research and Development.

The FDA approved beclomethasone dipropionate 40 mcg based on data from three double-blind, placebo-controlled studies of children aged 4-11 years. In those studies, once-daily beclomethasone dipropionate 40 mcg alleviated allergy symptoms in children with both seasonal and perennial allergic rhinitis with a minimum of adverse effects. The most common side effects were nosebleed and ulcers, which was “consistent with those seen in previous clinical studies of QNASL Nasal Aerosol,” according to a statement from the manufacturer.

QNASL40 mcg is expected to become available in February 2015.

[email protected]

The Food and Drug Administration has approved the 40-mcg dose of QNASL for use in the treatment of nasal symptoms associated with allergic rhinitis in children aged 4-11 years, making it the first waterless nasal allergy spray approved for use in children as young as 4 years old.

“Through the availability of QNASL [beclomethasone dipropionate] 40 mcg, we are aiming to aid children and their caregivers in better managing the burdensome symptoms associated with nasal allergies,” said Dr. Tushar Shah, senior vice president of Teva Global Respiratory Research and Development.

The FDA approved beclomethasone dipropionate 40 mcg based on data from three double-blind, placebo-controlled studies of children aged 4-11 years. In those studies, once-daily beclomethasone dipropionate 40 mcg alleviated allergy symptoms in children with both seasonal and perennial allergic rhinitis with a minimum of adverse effects. The most common side effects were nosebleed and ulcers, which was “consistent with those seen in previous clinical studies of QNASL Nasal Aerosol,” according to a statement from the manufacturer.

QNASL40 mcg is expected to become available in February 2015.

[email protected]

LAS VEGAS – Few conditions worry parents or school nurses more than when a child develops red eye, but how do you as the treating clinician know when to worry?

“Our challenge is to make the right diagnosis, not to worsen the problem, to figure when to refer, and to make that mother who had to take off from work to bring her child into the office – somehow we have to make her happy,” Dr. David B. Granet said at a pediatric update sponsored by the American Academy of Pediatrics California District 9.

Concomitant pain or photophobia typically means that something other than bacterial conjunctivitis is at play, said Dr. Granet, professor of ophthalmology and pediatrics at the University of California, San Diego. “Is there contact lens use?” he asked. “Is there proptosis or a history of trauma or injury? How long has it been going on? Most bacterial and viral infections will eventually go away. Is there a corneal opacity? Is there cellulitis, loss of vision, or herpes simplex virus?”

If parents call in suspecting that their child’s eye has been contaminated with a chemical, instruct them to irrigate the eye before they head to the emergency department, he advised. “Whoever’s answering the phone in your office ought to be able to separate out what’s worrisome and what’s not,” he said. “Like everything else we do, the history matters.”

For children who present to your office, consider “anything that can go wrong to make the eye red,” he continued, including nasolacrimal duct obstruction, adnexal disease, foreign body/trauma, uveitis, neoplasm, structural change, or conjunctivitis. “Has the vision changed? If so, that’s your vital sign for referral,” he said. “It’s generally a better sign to have both eyes involved with redness than just one. One eye involved means herpes simplex virus, uveitis, or trauma. Both eyes involved usually means infective or allergic conjunctivitis.”

The three most common conditions that cause a red or pink eye are allergic, bacterial, and viral conjunctivitis. Allergic conjunctivitis “is not just itching; that’s the symptom,” Dr. Granet said. “You get redness, swelling of the conjunctiva, lid edema, mucous discharge, and tearing. All of these occur when the patient rubs their eye. The best treatment for allergic conjunctivitis is avoidance of the allergen.”

He also recommended that affected children wash their hair before they go to sleep. “If their hair has been catching allergen all day long and they lie down on their pillow and start to roll [their head around in] it, that can cause a reaction,” he said.

Ketotifen fumarate (Zaditor) is an available over-the-counter treatment option, but olopatadine HCl (Pataday) is the most popular prescription written by pediatricians. “If you give any antihistamine, in low doses you start to prevent the release of histamine,” Dr. Granet said. “As the dose increases, you have a catastrophic event and you start to destruct the mast cell.”

Viral conjunctivitis usually affects older children and presents as a unilateral condition, then affects the fellow eye. It may be associated with pharyngitis and preauricular or submandibular adenopathy. Bacterial conjunctivitis, on the other hand, typically affects preschool-aged children, is often bilateral but can be unilateral, and yields mucopurulent discharge with matting. It is not associated with adenopathy, but it may be associated with otitis media, and it’s highly contagious. Topical antibiotic ointment therapy is indicated for bacterial conjunctivitis “not because this is a deadly disease, but because we want to reduce the chance for spread,” Dr. Granet said. “We know that communicable diseases are responsible for loss of 164 million school days each year. Additionally, there is a significant cost to a family when a parent misses work. Finally, if the diagnosis is in doubt, treatment with an antibiotic geared to work within a few days will help identify masquerade diseases early.”

Because of concerns about antibiotic resistance, fluoroquinolones are often the first choice for treating bacterial conjunctivitis. Dr. Granet led a multicenter comparison of moxifloxacin versus polymyxin B sulfate–trimethoprim ophthalmic solution in the speed of clinical efficacy for the treatment of bacterial conjunctivitis (J. Pediatr. Ophthalmol. Strabismus 2008;45:340-9). The investigators found that after day 2 of treatment, clinical cure was achieved by 81% of kids in the moxifloxacin group, compared with 44% of those in the polymyxin B sulfate–trimethoprim group. In addition, only 2.3% of kids in the moxifloxacin group were nonresponders, compared with 19.5% of those in the polymyxin B sulfate–trimethoprim group.

Common treatments for viral conjunctivitis include hygiene-related approaches like hand washing and not sharing towels and glasses. But these only prevent spread and don’t make the disease go away faster. The infection usually resolves in about 2 weeks.

Dr. Granet disclosed that he is a member of the speakers bureau for Alcon Labs and is a consultant for Diopsys.

[email protected]

On Twitter @dougbrunk

LAS VEGAS – Few conditions worry parents or school nurses more than when a child develops red eye, but how do you as the treating clinician know when to worry?

“Our challenge is to make the right diagnosis, not to worsen the problem, to figure when to refer, and to make that mother who had to take off from work to bring her child into the office – somehow we have to make her happy,” Dr. David B. Granet said at a pediatric update sponsored by the American Academy of Pediatrics California District 9.

Concomitant pain or photophobia typically means that something other than bacterial conjunctivitis is at play, said Dr. Granet, professor of ophthalmology and pediatrics at the University of California, San Diego. “Is there contact lens use?” he asked. “Is there proptosis or a history of trauma or injury? How long has it been going on? Most bacterial and viral infections will eventually go away. Is there a corneal opacity? Is there cellulitis, loss of vision, or herpes simplex virus?”

If parents call in suspecting that their child’s eye has been contaminated with a chemical, instruct them to irrigate the eye before they head to the emergency department, he advised. “Whoever’s answering the phone in your office ought to be able to separate out what’s worrisome and what’s not,” he said. “Like everything else we do, the history matters.”

For children who present to your office, consider “anything that can go wrong to make the eye red,” he continued, including nasolacrimal duct obstruction, adnexal disease, foreign body/trauma, uveitis, neoplasm, structural change, or conjunctivitis. “Has the vision changed? If so, that’s your vital sign for referral,” he said. “It’s generally a better sign to have both eyes involved with redness than just one. One eye involved means herpes simplex virus, uveitis, or trauma. Both eyes involved usually means infective or allergic conjunctivitis.”

The three most common conditions that cause a red or pink eye are allergic, bacterial, and viral conjunctivitis. Allergic conjunctivitis “is not just itching; that’s the symptom,” Dr. Granet said. “You get redness, swelling of the conjunctiva, lid edema, mucous discharge, and tearing. All of these occur when the patient rubs their eye. The best treatment for allergic conjunctivitis is avoidance of the allergen.”

He also recommended that affected children wash their hair before they go to sleep. “If their hair has been catching allergen all day long and they lie down on their pillow and start to roll [their head around in] it, that can cause a reaction,” he said.

Ketotifen fumarate (Zaditor) is an available over-the-counter treatment option, but olopatadine HCl (Pataday) is the most popular prescription written by pediatricians. “If you give any antihistamine, in low doses you start to prevent the release of histamine,” Dr. Granet said. “As the dose increases, you have a catastrophic event and you start to destruct the mast cell.”

Viral conjunctivitis usually affects older children and presents as a unilateral condition, then affects the fellow eye. It may be associated with pharyngitis and preauricular or submandibular adenopathy. Bacterial conjunctivitis, on the other hand, typically affects preschool-aged children, is often bilateral but can be unilateral, and yields mucopurulent discharge with matting. It is not associated with adenopathy, but it may be associated with otitis media, and it’s highly contagious. Topical antibiotic ointment therapy is indicated for bacterial conjunctivitis “not because this is a deadly disease, but because we want to reduce the chance for spread,” Dr. Granet said. “We know that communicable diseases are responsible for loss of 164 million school days each year. Additionally, there is a significant cost to a family when a parent misses work. Finally, if the diagnosis is in doubt, treatment with an antibiotic geared to work within a few days will help identify masquerade diseases early.”

Because of concerns about antibiotic resistance, fluoroquinolones are often the first choice for treating bacterial conjunctivitis. Dr. Granet led a multicenter comparison of moxifloxacin versus polymyxin B sulfate–trimethoprim ophthalmic solution in the speed of clinical efficacy for the treatment of bacterial conjunctivitis (J. Pediatr. Ophthalmol. Strabismus 2008;45:340-9). The investigators found that after day 2 of treatment, clinical cure was achieved by 81% of kids in the moxifloxacin group, compared with 44% of those in the polymyxin B sulfate–trimethoprim group. In addition, only 2.3% of kids in the moxifloxacin group were nonresponders, compared with 19.5% of those in the polymyxin B sulfate–trimethoprim group.

Common treatments for viral conjunctivitis include hygiene-related approaches like hand washing and not sharing towels and glasses. But these only prevent spread and don’t make the disease go away faster. The infection usually resolves in about 2 weeks.

Dr. Granet disclosed that he is a member of the speakers bureau for Alcon Labs and is a consultant for Diopsys.

[email protected]

On Twitter @dougbrunk

LAS VEGAS – Few conditions worry parents or school nurses more than when a child develops red eye, but how do you as the treating clinician know when to worry?

“Our challenge is to make the right diagnosis, not to worsen the problem, to figure when to refer, and to make that mother who had to take off from work to bring her child into the office – somehow we have to make her happy,” Dr. David B. Granet said at a pediatric update sponsored by the American Academy of Pediatrics California District 9.

Concomitant pain or photophobia typically means that something other than bacterial conjunctivitis is at play, said Dr. Granet, professor of ophthalmology and pediatrics at the University of California, San Diego. “Is there contact lens use?” he asked. “Is there proptosis or a history of trauma or injury? How long has it been going on? Most bacterial and viral infections will eventually go away. Is there a corneal opacity? Is there cellulitis, loss of vision, or herpes simplex virus?”

If parents call in suspecting that their child’s eye has been contaminated with a chemical, instruct them to irrigate the eye before they head to the emergency department, he advised. “Whoever’s answering the phone in your office ought to be able to separate out what’s worrisome and what’s not,” he said. “Like everything else we do, the history matters.”

For children who present to your office, consider “anything that can go wrong to make the eye red,” he continued, including nasolacrimal duct obstruction, adnexal disease, foreign body/trauma, uveitis, neoplasm, structural change, or conjunctivitis. “Has the vision changed? If so, that’s your vital sign for referral,” he said. “It’s generally a better sign to have both eyes involved with redness than just one. One eye involved means herpes simplex virus, uveitis, or trauma. Both eyes involved usually means infective or allergic conjunctivitis.”

The three most common conditions that cause a red or pink eye are allergic, bacterial, and viral conjunctivitis. Allergic conjunctivitis “is not just itching; that’s the symptom,” Dr. Granet said. “You get redness, swelling of the conjunctiva, lid edema, mucous discharge, and tearing. All of these occur when the patient rubs their eye. The best treatment for allergic conjunctivitis is avoidance of the allergen.”

He also recommended that affected children wash their hair before they go to sleep. “If their hair has been catching allergen all day long and they lie down on their pillow and start to roll [their head around in] it, that can cause a reaction,” he said.

Ketotifen fumarate (Zaditor) is an available over-the-counter treatment option, but olopatadine HCl (Pataday) is the most popular prescription written by pediatricians. “If you give any antihistamine, in low doses you start to prevent the release of histamine,” Dr. Granet said. “As the dose increases, you have a catastrophic event and you start to destruct the mast cell.”

Viral conjunctivitis usually affects older children and presents as a unilateral condition, then affects the fellow eye. It may be associated with pharyngitis and preauricular or submandibular adenopathy. Bacterial conjunctivitis, on the other hand, typically affects preschool-aged children, is often bilateral but can be unilateral, and yields mucopurulent discharge with matting. It is not associated with adenopathy, but it may be associated with otitis media, and it’s highly contagious. Topical antibiotic ointment therapy is indicated for bacterial conjunctivitis “not because this is a deadly disease, but because we want to reduce the chance for spread,” Dr. Granet said. “We know that communicable diseases are responsible for loss of 164 million school days each year. Additionally, there is a significant cost to a family when a parent misses work. Finally, if the diagnosis is in doubt, treatment with an antibiotic geared to work within a few days will help identify masquerade diseases early.”

Because of concerns about antibiotic resistance, fluoroquinolones are often the first choice for treating bacterial conjunctivitis. Dr. Granet led a multicenter comparison of moxifloxacin versus polymyxin B sulfate–trimethoprim ophthalmic solution in the speed of clinical efficacy for the treatment of bacterial conjunctivitis (J. Pediatr. Ophthalmol. Strabismus 2008;45:340-9). The investigators found that after day 2 of treatment, clinical cure was achieved by 81% of kids in the moxifloxacin group, compared with 44% of those in the polymyxin B sulfate–trimethoprim group. In addition, only 2.3% of kids in the moxifloxacin group were nonresponders, compared with 19.5% of those in the polymyxin B sulfate–trimethoprim group.

Common treatments for viral conjunctivitis include hygiene-related approaches like hand washing and not sharing towels and glasses. But these only prevent spread and don’t make the disease go away faster. The infection usually resolves in about 2 weeks.

Dr. Granet disclosed that he is a member of the speakers bureau for Alcon Labs and is a consultant for Diopsys.

[email protected]

On Twitter @dougbrunk

The reported link between early life exposure to acetaminophen and the development of asthma in children is “weak” and “overstated” based on currently available evidence, according to a report published by the Archives of Disease in Childhood.

In a review of currently available data culled from Embase and PubMed databases, 1,192 relevant studies conducted between 1967 and 2013 were analyzed, of which 11 were included for analysis. Of these 11 studies, 5 found “increased odds” that exposure to acetaminophen during the first trimester of pregnancy could lead to development of asthma (pooled odds ratio, 1.39); however, there was a high degree of between-study heterogeneity among the trials (I² = 64.2%, P = .03), reported Dr. M. Cheelo of the University of Melbourne, and associates.

Creatas Images

Of those five, only two studies examined the effects of acetaminophen exposure during the second trimester, but attained widely disparate results: Study one reported an OR of 1.06, while the other reported an OR of 2.15, with I² = 80%. Two studies also tested acetaminophen exposure during the third trimester and found a “weak association,” with a pooled OR of 1.17. Three studies look at acetaminophen exposure through an entire pregnancy, but all had “significant heterogeneity” in their findings (OR = 1.65, 1.22, and 0.74; I² = 89%). Only one study that was examined adjusted for respiratory tract infections during pregnancy, but according to the authors, “all studies that adjusted for early life respiratory tract infections found a reduction in the association between [acetaminophen] exposure and subsequent childhood asthma” (Arch. Dis. Child. 2014 [doi:10.1136/archdischild-2012-303043]).

The other 6 of the 11 total studies examined acetaminophen exposure over the first 2 years of life. Three of these studies found a “weak positive association,” as did four studies directly comparing children with and without acetaminophen exposure. All but one study adjusted results for respiratory tract infections during pregnancy, which caused a “moderate attenuation of the association between frequency of [acetaminophen] intake and childhood asthma.” Consequently, investigators concluded that “evidence of an association between early life [acetaminophen] and asthma is often overstated, and there is currently insufficient evidence to support changing guidelines in the use of this medicine.”

The authors reported no relevant financial conflicts of interest.

[email protected]

The reported link between early life exposure to acetaminophen and the development of asthma in children is “weak” and “overstated” based on currently available evidence, according to a report published by the Archives of Disease in Childhood.

In a review of currently available data culled from Embase and PubMed databases, 1,192 relevant studies conducted between 1967 and 2013 were analyzed, of which 11 were included for analysis. Of these 11 studies, 5 found “increased odds” that exposure to acetaminophen during the first trimester of pregnancy could lead to development of asthma (pooled odds ratio, 1.39); however, there was a high degree of between-study heterogeneity among the trials (I² = 64.2%, P = .03), reported Dr. M. Cheelo of the University of Melbourne, and associates.

Creatas Images

Of those five, only two studies examined the effects of acetaminophen exposure during the second trimester, but attained widely disparate results: Study one reported an OR of 1.06, while the other reported an OR of 2.15, with I² = 80%. Two studies also tested acetaminophen exposure during the third trimester and found a “weak association,” with a pooled OR of 1.17. Three studies look at acetaminophen exposure through an entire pregnancy, but all had “significant heterogeneity” in their findings (OR = 1.65, 1.22, and 0.74; I² = 89%). Only one study that was examined adjusted for respiratory tract infections during pregnancy, but according to the authors, “all studies that adjusted for early life respiratory tract infections found a reduction in the association between [acetaminophen] exposure and subsequent childhood asthma” (Arch. Dis. Child. 2014 [doi:10.1136/archdischild-2012-303043]).

The other 6 of the 11 total studies examined acetaminophen exposure over the first 2 years of life. Three of these studies found a “weak positive association,” as did four studies directly comparing children with and without acetaminophen exposure. All but one study adjusted results for respiratory tract infections during pregnancy, which caused a “moderate attenuation of the association between frequency of [acetaminophen] intake and childhood asthma.” Consequently, investigators concluded that “evidence of an association between early life [acetaminophen] and asthma is often overstated, and there is currently insufficient evidence to support changing guidelines in the use of this medicine.”

The authors reported no relevant financial conflicts of interest.

[email protected]

The reported link between early life exposure to acetaminophen and the development of asthma in children is “weak” and “overstated” based on currently available evidence, according to a report published by the Archives of Disease in Childhood.

In a review of currently available data culled from Embase and PubMed databases, 1,192 relevant studies conducted between 1967 and 2013 were analyzed, of which 11 were included for analysis. Of these 11 studies, 5 found “increased odds” that exposure to acetaminophen during the first trimester of pregnancy could lead to development of asthma (pooled odds ratio, 1.39); however, there was a high degree of between-study heterogeneity among the trials (I² = 64.2%, P = .03), reported Dr. M. Cheelo of the University of Melbourne, and associates.

Creatas Images

Of those five, only two studies examined the effects of acetaminophen exposure during the second trimester, but attained widely disparate results: Study one reported an OR of 1.06, while the other reported an OR of 2.15, with I² = 80%. Two studies also tested acetaminophen exposure during the third trimester and found a “weak association,” with a pooled OR of 1.17. Three studies look at acetaminophen exposure through an entire pregnancy, but all had “significant heterogeneity” in their findings (OR = 1.65, 1.22, and 0.74; I² = 89%). Only one study that was examined adjusted for respiratory tract infections during pregnancy, but according to the authors, “all studies that adjusted for early life respiratory tract infections found a reduction in the association between [acetaminophen] exposure and subsequent childhood asthma” (Arch. Dis. Child. 2014 [doi:10.1136/archdischild-2012-303043]).

The other 6 of the 11 total studies examined acetaminophen exposure over the first 2 years of life. Three of these studies found a “weak positive association,” as did four studies directly comparing children with and without acetaminophen exposure. All but one study adjusted results for respiratory tract infections during pregnancy, which caused a “moderate attenuation of the association between frequency of [acetaminophen] intake and childhood asthma.” Consequently, investigators concluded that “evidence of an association between early life [acetaminophen] and asthma is often overstated, and there is currently insufficient evidence to support changing guidelines in the use of this medicine.”

The authors reported no relevant financial conflicts of interest.

[email protected]

[Courtesy of Arizona Asthma & Allergy Institute]

Click Here for Free CE/CME on Vocal Cord Dysfunction: Unmasking the Asthma Pretender

[Courtesy of Arizona Asthma & Allergy Institute]

Click Here for Free CE/CME on Vocal Cord Dysfunction: Unmasking the Asthma Pretender

[Courtesy of Arizona Asthma & Allergy Institute]

Click Here for Free CE/CME on Vocal Cord Dysfunction: Unmasking the Asthma Pretender

CE/CME No: CR-1412

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Discuss the evolution in thinking about the pathogenesis of and treatment for vocal cord dysfunction (VCD).
• Describe the three primary functions of the healthy vocal cords.
• List the conditions or factors that may trigger VCD.
• Explain how to differentiate VCD from asthma.
• Develop a treatment plan for VCD that addresses both patient-specific VCD triggers and management of symptomatic episodes.

FACULTY
Linda S. MacConnell is an Assistant Professor in the Department of Physician Assistant Studies and Randy D. Danielsen is a Professor and Dean at the Arizona School of Health Sciences, AT Still University, Mesa. Ms. MacConnell is also a clinical PA affiliated with Enticare, an otolaryngology practice in Chandler, Arizona. Susan Symington is a clinical PA with the Arizona Asthma & Allergy Institute, with which Dr. Danielsen is also affiliated.
Linda MacConnell and Randy Danielsen have no significant financial relationships to disclose. Susan Symington is a member of the speaker’s bureau for Teva Respiratory and Thermo Fisher Scientific, Inc.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of December 2014.

Article begins on next page >>

The symptoms of vocal cord dysfunction (VCD) can be mistaken for those
of asthma or other respiratory illnesses. As a result, VCD is often misdiagnosed,
leading to unnecessary, ineffective, costly, or even dangerous treatment. Here are
the facts that will enable you to avoid making an erroneous diagnosis, choosing
potentially harmful treatment, and delaying effective treatment.

A 33-year-old oncology nurse, JD, had moved from Seattle to Phoenix about six months earlier for a job opportunity. Shortly after starting her new job, she had developed intermittent dyspnea on exertion, with a cough lasting several minutes at a time, along with a sensation of heaviness over the larynx and a choking sensation. These symptoms were precipitated by gastroesophageal reflux disease (GERD), postnasal drainage, stress, and significant environmental change (ie, Seattle to Phoenix). She noticed that, since moving to Phoenix, she frequently cleared her throat but denied any hoarseness, dysphagia, chest tightness, chest pain, or wheezing. She noted nasal congestion and clear nasal discharge on exposure to inhaled irritants (eg, woodstove smoke) and strong fragrances (eg, perfume or cologne).

On physical examination, the patient was alert, oriented, and in no acute distress. She was coughing intermittently but was able to speak in complete sentences. No stridor or dyspnea was noted, either on exertion (jogging in place) or at rest.

HEENT examination was normal, with no scalp lesions or tenderness; face, symmetric; light reflex, symmetric; conjunctivae, clear; sclera white, without lesions or redness; pupils, equal, reactive to light and accommodation; tympanic membranes and canals, clear with intact landmarks; no nasal deformities; nasal mucosa, mildly erythematous with mild engorgement of the turbinates; no nasal polyps seen; nasal septum midline without perforation; no sinus tenderness on percussion; pharynx, clear without exudate; uvula rises on phonation; and oral mucosa and gingivae, pink without lesions. Neck was supple without masses or thyromegaly, and trachea was midline. Lungs were clear to auscultation with normal respiratory movement and no accessory muscle use, with normal anteroposterior diameter. Heart examination revealed regular rate and rhythm, without murmur, clicks, or gallops.

Examination of the skin was normal, without rashes, hives, swelling, petechiae, or significant ecchymosis. There was no palpable cervical, supraclavicular, or axillary adenopathy.

Results of laboratory studies included a normal complete blood count with differential and a normal IgE level of 46.3 IU/mL. Spirometry testing revealed normal values without obstruction; however, there was a flattening of the inspiratory flow loop, with no reversibility after bronchodilator, which was highly suggestive of vocal cord dysfunction (VCD). Perennial nonallergic rhinitis (formerly called vasomotor rhinitis) was confirmed because the patient experienced fewer symptoms to perfume after nasal corticosteroid use. The patient’s GERD was generally well controlled with esomeprazole but was likely a contributing factor to her vocal cord symptoms.

On laryngoscopy, abnormal vocal cord movement toward the midline during both inspiration and expiration was visualized, confirming the diagnosis of VCD.

BACKGROUND
VCD is a partial upper airway obstruction caused by paradoxical adduction (medial movement) of the vocal cords.¹ Although it is primarily associated with inspiration, it sometimes manifests during expiration as well.

The true incidence of VCD is uncertain; different studies have found incidence rates varying from 2% to 27%, with higher rates in patients with asthma.^1,2 However, highlighting the risk for misdiagnosis, some 10% of patients evaluated for asthma unresponsive to aggressive treatment were found, in fact, to have VCD alone.²

Similarly, although VCD is generally more common in women than in men, the reported female-to-male ratio has varied from 2:1 to 4:1.^1,2,4 Some reports suggest that VCD is seen more frequently in younger women, with average ages at diagnosis of 14.5 in adolescents and 33 in adults.^2,3 Others identify a broader age range, with most patients older than 50.⁴

Historically, VCD has been known by a variety of names and has been observed clinically since 1842. In that year, Dunglison referred to it as hysteric croup, describing a disorder of the laryngeal muscles brought on by “hysteria.”⁵ Later, Mackenzie was able to visualize adduction of the vocal cords during inspiration in patients with stridor by using a laryngoscope.⁶ Osler demonstrated his understanding of the condition in 1902, stating, “Spasm of muscles may occur with violent inspiratory effort and great distress, and may even lead to cyanosis. Extraordinary cries may be produced either inspiratory or expiratory.”⁷

More recently, in 1974, Patterson et al reported finding laryngoscopic evidence of VCD, which they termed Munchausen’s stridor.⁸ They used this descriptor to report on the case of a young woman with 15 hospital admissions for this condition. At the time, the etiology of the condition was believed to be largely psychologic, and its evaluation was consigned to psychiatrists and other mental health practitioners.

As laryngoscopy became more widely available in the 1970s and 1980s, diagnosis of VCD increased, although the condition remains underrecognized.⁹ Ibrahim et al suggest that primary care clinicians may not be as aware of VCD as they should be and may not consider laryngoscopy for possible VCD in patients whose asthma is poorly controlled.²

Disagreement persists with regard to the preferred name for the condition. Because numerous disorders involve abnormal vocal cord function, Christopher proposed moving away from the broad term VCD and toward a more descriptive term: paradoxical vocal fold motion (PVFM) disorder.¹⁰ Interestingly, use of the two terms seems to be divided along specialty lines: VCD is preferred by allergy, pulmonology, and mental health specialists, while PVFM is favored by otolaryngology specialists and speech-language pathologists.¹¹

Further complicating awareness and recognition of VCD is its longstanding reputation as a psychologic disorder. In fact, the paradigm has shifted away from defining VCD as a purely psychopathologic entity to the identification of numerous functional etiologies for the disorder. This, however, has resulted in many new terms to describe the condition, including nonorganic upper airway obstruction, pseudoasthma, irritable larynx syndrome, factitious asthma, spasmodic croup, functional upper airway obstruction, episodic laryngeal dyskinesia, functional laryngeal obstruction, functional laryngeal stridor, and episodic paroxysmal laryngospasm.¹

Regardless of its name, an understanding of VCD is essential for both primary care and specialty clinicians because of its frequent misdiagnosis as asthma, allergies, or severe upper airway obstruction. When it is misdiagnosed as asthma, aggressive asthma treatments—to which VCD does not respond—may be prescribed, including high-dose inhaled and systemic corticosteroids and bronchodilators. Patients may experience multiple emergency department (ED) visits and hospitalizations and, in some cases, may be subjected to tracheostomies and intubation.

Continue for vocal cord physiology and functions >>

VOCAL CORD PHYSIOLOGY AND FUNCTIONS
The vocal cords are located within the larynx. Abduction, or opening, of the cords is controlled by the posterior cricoarytenoid muscle; adduction, or closing, occurs via contraction of the lateral cricoarytenoid muscle. These muscles are innervated by the recurrent laryngeal nerve to control the width of the space—the rima glottidis—between the cords. During inspiration, the glottis opens; during expiration, it narrows but remains open.¹²

The vocal cords are involved in three main functions: protection of the airway, respiration, and phonation (vocal production). These functions are at least partially controlled involuntarily by brain stem reflexes; however, only airway protection—the most important of these functions—is reflexive and involuntary.¹² Respiration may be controlled voluntarily, and phonation is primarily voluntary. Closure of the vocal cords is under the control of the laryngeal nerve branches of the vagal nerve.^12,13

The vocal cords normally abduct during inspiration to allow air to pass through them into the trachea and the lungs. Sniffing, puffing, snuffling, and panting also cause the vocal cords to abduct. The vocal cords adduct with phonation (talking, singing), coughing, clearing the throat, performing the Valsalva maneuver, and swallowing. During expiration, 10% to 40% adduction is considered normal.¹⁴

VOCAL CORD DYSFUNCTION
Pathogenesis and etiology
VCD is a nonspecific term, and a number of factors may be involved in its development.¹⁵ Although the precise cause of VCD is unknown, it is believed to result from laryngeal hyperresponsiveness. This exaggerated responsiveness may be prompted by irritant and nonirritant triggers of the sensory receptors in the larynx, trachea, and large airways that mediate cough and glottis closure reflexes.¹⁶

VCD may be among a group of airway disorders triggered by occupational exposures, including irritants and psychologic stressors. For example, occupationally triggered VCD was diagnosed in rescue, recovery, and cleanup workers at the World Trade Center disaster site.⁴

A history of childhood sexual abuse has also been associated by some researchers with the development of VCD. For example, Freedman et al reported that, of 47 patients with VCD, 14 identified such a history and five were suspected of having been sexually abused as children.¹⁷

Paradoxical movement of the vocal cords causes them to close when they should open. (Click here for a video on normal and abnormal vocal cord movement.) VCD generally occurs during inspiration, causing obstruction of the incoming air through the larynx. Symptoms of VCD frequently include dyspnea, coughing, wheezing, hoarseness, and tightness or pain in the throat.

Examination of the flow-volume loops recorded when a patient experiences “wheezing” during spirometry testing reveals a flattened inspiratory loop, indicating a decrease of airflow into the lungs (see Figure 1).^13,16 “Wheezing” is actually a misnomer in this situation because the term typically refers to sounds that occur during expiration.

Triggers
Physiologic, psychologic, and neurologic factors may all contribute to VCD.^1,15 Conditions that can trigger VCD include
• Asthma
• Postnasal drip
• Recent upper respiratory illness (URI)
• Talking, singing
• Exercise
• Cough
• Voice strain
• Stress, anxiety, tension, elevated emotions
• Common irritants (eg, strong smells)
• Airborne irritants
• Rhinosinusitis
• GERD
• Use of certain medications
Identification of a particular patient’s triggers is key to successful management of VCD.

PATIENT PRESENTATION
Although there is no “typical” patient with VCD, the condition occurs more frequently in women, with the most common age at onset between 20 and 40 years. However, VCD has been seen in very young children and in adults as old as 83, and its diagnosis in the pediatric population is increasing.¹⁸

The patient may present with complaints of atypical chest pain, throat tightness, stridor, choking, difficult vocalization, cough and sometimes dysphagia, GERD, or rhinosinusitis (see Table 1). These signs and symptoms may occur without provocation, or patients may relate a history of triggers such as anxiety, irritant exposure, or exercise. In fact, about 14% of VCD is associated with exercise, particularly in young female athletes who experience shortness of breath and even stridor with exercise.¹⁹

A characteristic finding on physical examination is inspiratory stridor, along with respiratory distress.²⁰ The stridor is best auscultated not over the anterior chest wall but over the tracheal area of the anterior neck.

Continue for differential diagnosis >>

DIFFERENTIAL DIAGNOSIS
Distinguishing VCD from other disorders can be challenging. Differential diagnosis should include
• Non–vocal cord adduction disorders, such as thyroid goiter, upper airway hemorrhage, caustic ingestion, neoplastic disorders, rheumatoid cricoarytenoid arthritis, pharyngeal abscess, angioedema, pulmonary embolus²¹
• Anatomic defects (eg, laryngomalacia, subglottic stenosis)
• Tracheal masses (eg, enlarged thyroid gland)
• Vocal cord polyps
• Laryngospasm
• Vocal cord paresis
• Neurologic causes (eg, brain stem compression, severe cortical injury, nuclear or lower motor neuron injury, movement disorders)
• Nonorganic causes (eg, factitious symptoms or malingering; conversion disorder)²²
• Reactive airway disease.
Some disorders are easier to distinguish from VCD than others. For example, although laryngospasm may produce similar symptoms, episodes are brief, lasting seconds to minutes; VCD episodes may last hours to days.

Asthma
Even the most astute clinician will be unable to obtain adequate information from the patient history to differentiate VCD from asthma. There is a significant overlap of symptoms—shortness of breath, cough, wheezing—and frequently, the diseases coexist. History is often negative for chest pain, but it is common for patients with VCD, when asked to describe their symptoms, to report chest tightness. The clinician therefore needs to ask the patient to point to where the tightness is felt—in the chest or in the neck over the laryngeal area—to distinguish the source.

Asthma symptoms usually increase over a few hours, days, or weeks but respond to medications that open the airway and reduce inflammation (inhaled β-agonists and corticosteroids). VCD symptoms usually occur or decrease suddenly and do not respond well to traditional asthma treatments.

Other differences between asthma and VCD symptoms include voice changes and time of day when symptoms occur. The person with VCD will experience voice changes, such as hoarseness, as well as prolonged coughing episodes. Patients with asthma may awaken at night because of breathlessness, while most patients with VCD experience symptoms only during the day.

The diagnosis is generally confirmed if VCD is seen on direct laryngoscopic visualization during a symptomatic episode. In terms of adduction, the anterior cords will appear normal, but the posterior portion of the cords will display the classic “glottis chink” (see Figure 2).⁹

If the diagnosis is in question, videostroboscopy, a technique that provides a magnified slow-motion view of vocal cord vibration, can help identify or exclude pathologic conditions of the vocal cords.²³

Convincing the patient of the validity of the diagnosis may be problematic if the patient has been previously diagnosed with and treated for another condition. The diagnosis should be explained and the patient counseled what appropriate care for VCD entails (see discussion under “Patient education and self-care”).

TREATMENT
Acute episode
During an acute VCD episode, offering the patient calm reassurance can be effective in resolving the episode. Simple breathing guidance may also be beneficial; instructing the patient to breathe rapidly and shallowly (ie, pant) can result in immediate resolution of symptoms.²⁴ The patient can be advised to utilize other techniques, such as diaphragmatic breathing, breathing through the nose, breathing through a straw, pursed-lip breathing, and exhaling with a hissing sound.²⁵

Long-term management
Although various strategies are employed in the management of VCD, well-designed studies on which to base treatment decisions have not been performed. Of course, control and management of possible underlying triggers or disorders should be implemented. Because etiology is rarely known, treatment for VCD is generally empiric.

Evidence does exist, however, to suggest that voice therapy, the treatment of choice for muscle tension dysphonia, is also effective for VCD. Speech therapy with specific voice and breathing exercises can enable the patient to manage the condition, thereby reducing ED visits, hospitalizations, and treatment costs.²⁶

Patient education and self-care
Patient education is a critical component of VCD management. The clinician should explain the functions of the larynx to the patient, including the normal functioning of the vocal cords during respiration, speaking, swallowing, coughing, throat clearing, and breath holding. It may also enhance patients’ understanding of VCD to view their diagnostic laryngoscopy or videostroboscopy films.²¹

The patient should be advised to rest the voice, hydrate, utilize sialagogues (lozenges, gum) to stimulate salivation, reduce exposure to triggers when possible, and decrease stress. She should be encouraged to track VCD triggers by documenting what she is doing, where, and when, at the time of a VCD episode.

Two exercises—“paused breathing” and “belly breathing”—can be used by patients to learn how to relax the vocal cords (see “Patient Handout”). Patients should practice these exercises three times a day so that they can be easily recalled and performed during VCD episodes.

Continue for outcomes >>

OUTCOMES
Little is known about long-term outcomes for patients with VCD. The current literature consists of poorly described and conflicting case reports and results of small trials. Although documentation is lacking, the authors agree that, by educating the patient about the diagnosis, teaching effective VCD management strategies, and referring patients for voice therapy, clinicians can help patients achieve signicant improvement. Further investigation is needed to enhance our knowledge of the causes of VCD and to research additional diagnostic modalities and treatments.²

CASE PATIENT
After diagnosing VCD, the clinician explained the normal functioning of the vocal cords and how certain factors may cause them to close during inspiration. The patient then understood why bronchodilator therapy had failed to relieve her symptoms. She was counseled to continue her inhaled nasal steroid and proton pump inhibitor for her perennial nonallergic rhinitis and GERD, respectively, because these conditions may trigger her VCD, and to take steps to manage her stress. She learned breathing techniques to alleviate acute episodes of VCD and was informed of the option of voice therapy with a speech therapist if needed.

At six-week follow-up, the patient reported that she was complying with her medication regimen, had made an effort to relax more, and had experienced no acute attacks of VCD since her last visit.

CONCLUSION
Patients with symptoms suggestive of VCD require a thorough evaluation, including laryngoscopic examination, to ensure accurate diagnosis and avoid a too-common misdiagnosis. Primary care clinicians should know about VCD and, if not trained in the performance of flexible laryngoscopy, should refer the symptomatic patient to a specialist for appropriate work-up.

CE/CME No: CR-1412

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Discuss the evolution in thinking about the pathogenesis of and treatment for vocal cord dysfunction (VCD).
• Describe the three primary functions of the healthy vocal cords.
• List the conditions or factors that may trigger VCD.
• Explain how to differentiate VCD from asthma.
• Develop a treatment plan for VCD that addresses both patient-specific VCD triggers and management of symptomatic episodes.

FACULTY
Linda S. MacConnell is an Assistant Professor in the Department of Physician Assistant Studies and Randy D. Danielsen is a Professor and Dean at the Arizona School of Health Sciences, AT Still University, Mesa. Ms. MacConnell is also a clinical PA affiliated with Enticare, an otolaryngology practice in Chandler, Arizona. Susan Symington is a clinical PA with the Arizona Asthma & Allergy Institute, with which Dr. Danielsen is also affiliated.
Linda MacConnell and Randy Danielsen have no significant financial relationships to disclose. Susan Symington is a member of the speaker’s bureau for Teva Respiratory and Thermo Fisher Scientific, Inc.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of December 2014.

Article begins on next page >>

The symptoms of vocal cord dysfunction (VCD) can be mistaken for those
of asthma or other respiratory illnesses. As a result, VCD is often misdiagnosed,
leading to unnecessary, ineffective, costly, or even dangerous treatment. Here are
the facts that will enable you to avoid making an erroneous diagnosis, choosing
potentially harmful treatment, and delaying effective treatment.

A 33-year-old oncology nurse, JD, had moved from Seattle to Phoenix about six months earlier for a job opportunity. Shortly after starting her new job, she had developed intermittent dyspnea on exertion, with a cough lasting several minutes at a time, along with a sensation of heaviness over the larynx and a choking sensation. These symptoms were precipitated by gastroesophageal reflux disease (GERD), postnasal drainage, stress, and significant environmental change (ie, Seattle to Phoenix). She noticed that, since moving to Phoenix, she frequently cleared her throat but denied any hoarseness, dysphagia, chest tightness, chest pain, or wheezing. She noted nasal congestion and clear nasal discharge on exposure to inhaled irritants (eg, woodstove smoke) and strong fragrances (eg, perfume or cologne).

On physical examination, the patient was alert, oriented, and in no acute distress. She was coughing intermittently but was able to speak in complete sentences. No stridor or dyspnea was noted, either on exertion (jogging in place) or at rest.

HEENT examination was normal, with no scalp lesions or tenderness; face, symmetric; light reflex, symmetric; conjunctivae, clear; sclera white, without lesions or redness; pupils, equal, reactive to light and accommodation; tympanic membranes and canals, clear with intact landmarks; no nasal deformities; nasal mucosa, mildly erythematous with mild engorgement of the turbinates; no nasal polyps seen; nasal septum midline without perforation; no sinus tenderness on percussion; pharynx, clear without exudate; uvula rises on phonation; and oral mucosa and gingivae, pink without lesions. Neck was supple without masses or thyromegaly, and trachea was midline. Lungs were clear to auscultation with normal respiratory movement and no accessory muscle use, with normal anteroposterior diameter. Heart examination revealed regular rate and rhythm, without murmur, clicks, or gallops.

Examination of the skin was normal, without rashes, hives, swelling, petechiae, or significant ecchymosis. There was no palpable cervical, supraclavicular, or axillary adenopathy.

Results of laboratory studies included a normal complete blood count with differential and a normal IgE level of 46.3 IU/mL. Spirometry testing revealed normal values without obstruction; however, there was a flattening of the inspiratory flow loop, with no reversibility after bronchodilator, which was highly suggestive of vocal cord dysfunction (VCD). Perennial nonallergic rhinitis (formerly called vasomotor rhinitis) was confirmed because the patient experienced fewer symptoms to perfume after nasal corticosteroid use. The patient’s GERD was generally well controlled with esomeprazole but was likely a contributing factor to her vocal cord symptoms.

On laryngoscopy, abnormal vocal cord movement toward the midline during both inspiration and expiration was visualized, confirming the diagnosis of VCD.

BACKGROUND
VCD is a partial upper airway obstruction caused by paradoxical adduction (medial movement) of the vocal cords.¹ Although it is primarily associated with inspiration, it sometimes manifests during expiration as well.

The true incidence of VCD is uncertain; different studies have found incidence rates varying from 2% to 27%, with higher rates in patients with asthma.^1,2 However, highlighting the risk for misdiagnosis, some 10% of patients evaluated for asthma unresponsive to aggressive treatment were found, in fact, to have VCD alone.²

Similarly, although VCD is generally more common in women than in men, the reported female-to-male ratio has varied from 2:1 to 4:1.^1,2,4 Some reports suggest that VCD is seen more frequently in younger women, with average ages at diagnosis of 14.5 in adolescents and 33 in adults.^2,3 Others identify a broader age range, with most patients older than 50.⁴

Historically, VCD has been known by a variety of names and has been observed clinically since 1842. In that year, Dunglison referred to it as hysteric croup, describing a disorder of the laryngeal muscles brought on by “hysteria.”⁵ Later, Mackenzie was able to visualize adduction of the vocal cords during inspiration in patients with stridor by using a laryngoscope.⁶ Osler demonstrated his understanding of the condition in 1902, stating, “Spasm of muscles may occur with violent inspiratory effort and great distress, and may even lead to cyanosis. Extraordinary cries may be produced either inspiratory or expiratory.”⁷

More recently, in 1974, Patterson et al reported finding laryngoscopic evidence of VCD, which they termed Munchausen’s stridor.⁸ They used this descriptor to report on the case of a young woman with 15 hospital admissions for this condition. At the time, the etiology of the condition was believed to be largely psychologic, and its evaluation was consigned to psychiatrists and other mental health practitioners.

As laryngoscopy became more widely available in the 1970s and 1980s, diagnosis of VCD increased, although the condition remains underrecognized.⁹ Ibrahim et al suggest that primary care clinicians may not be as aware of VCD as they should be and may not consider laryngoscopy for possible VCD in patients whose asthma is poorly controlled.²

Disagreement persists with regard to the preferred name for the condition. Because numerous disorders involve abnormal vocal cord function, Christopher proposed moving away from the broad term VCD and toward a more descriptive term: paradoxical vocal fold motion (PVFM) disorder.¹⁰ Interestingly, use of the two terms seems to be divided along specialty lines: VCD is preferred by allergy, pulmonology, and mental health specialists, while PVFM is favored by otolaryngology specialists and speech-language pathologists.¹¹

Further complicating awareness and recognition of VCD is its longstanding reputation as a psychologic disorder. In fact, the paradigm has shifted away from defining VCD as a purely psychopathologic entity to the identification of numerous functional etiologies for the disorder. This, however, has resulted in many new terms to describe the condition, including nonorganic upper airway obstruction, pseudoasthma, irritable larynx syndrome, factitious asthma, spasmodic croup, functional upper airway obstruction, episodic laryngeal dyskinesia, functional laryngeal obstruction, functional laryngeal stridor, and episodic paroxysmal laryngospasm.¹

Regardless of its name, an understanding of VCD is essential for both primary care and specialty clinicians because of its frequent misdiagnosis as asthma, allergies, or severe upper airway obstruction. When it is misdiagnosed as asthma, aggressive asthma treatments—to which VCD does not respond—may be prescribed, including high-dose inhaled and systemic corticosteroids and bronchodilators. Patients may experience multiple emergency department (ED) visits and hospitalizations and, in some cases, may be subjected to tracheostomies and intubation.

Continue for vocal cord physiology and functions >>

VOCAL CORD PHYSIOLOGY AND FUNCTIONS
The vocal cords are located within the larynx. Abduction, or opening, of the cords is controlled by the posterior cricoarytenoid muscle; adduction, or closing, occurs via contraction of the lateral cricoarytenoid muscle. These muscles are innervated by the recurrent laryngeal nerve to control the width of the space—the rima glottidis—between the cords. During inspiration, the glottis opens; during expiration, it narrows but remains open.¹²

The vocal cords are involved in three main functions: protection of the airway, respiration, and phonation (vocal production). These functions are at least partially controlled involuntarily by brain stem reflexes; however, only airway protection—the most important of these functions—is reflexive and involuntary.¹² Respiration may be controlled voluntarily, and phonation is primarily voluntary. Closure of the vocal cords is under the control of the laryngeal nerve branches of the vagal nerve.^12,13

The vocal cords normally abduct during inspiration to allow air to pass through them into the trachea and the lungs. Sniffing, puffing, snuffling, and panting also cause the vocal cords to abduct. The vocal cords adduct with phonation (talking, singing), coughing, clearing the throat, performing the Valsalva maneuver, and swallowing. During expiration, 10% to 40% adduction is considered normal.¹⁴

VOCAL CORD DYSFUNCTION
Pathogenesis and etiology
VCD is a nonspecific term, and a number of factors may be involved in its development.¹⁵ Although the precise cause of VCD is unknown, it is believed to result from laryngeal hyperresponsiveness. This exaggerated responsiveness may be prompted by irritant and nonirritant triggers of the sensory receptors in the larynx, trachea, and large airways that mediate cough and glottis closure reflexes.¹⁶

VCD may be among a group of airway disorders triggered by occupational exposures, including irritants and psychologic stressors. For example, occupationally triggered VCD was diagnosed in rescue, recovery, and cleanup workers at the World Trade Center disaster site.⁴

A history of childhood sexual abuse has also been associated by some researchers with the development of VCD. For example, Freedman et al reported that, of 47 patients with VCD, 14 identified such a history and five were suspected of having been sexually abused as children.¹⁷

Paradoxical movement of the vocal cords causes them to close when they should open. (Click here for a video on normal and abnormal vocal cord movement.) VCD generally occurs during inspiration, causing obstruction of the incoming air through the larynx. Symptoms of VCD frequently include dyspnea, coughing, wheezing, hoarseness, and tightness or pain in the throat.

Examination of the flow-volume loops recorded when a patient experiences “wheezing” during spirometry testing reveals a flattened inspiratory loop, indicating a decrease of airflow into the lungs (see Figure 1).^13,16 “Wheezing” is actually a misnomer in this situation because the term typically refers to sounds that occur during expiration.

Triggers
Physiologic, psychologic, and neurologic factors may all contribute to VCD.^1,15 Conditions that can trigger VCD include
• Asthma
• Postnasal drip
• Recent upper respiratory illness (URI)
• Talking, singing
• Exercise
• Cough
• Voice strain
• Stress, anxiety, tension, elevated emotions
• Common irritants (eg, strong smells)
• Airborne irritants
• Rhinosinusitis
• GERD
• Use of certain medications
Identification of a particular patient’s triggers is key to successful management of VCD.

PATIENT PRESENTATION
Although there is no “typical” patient with VCD, the condition occurs more frequently in women, with the most common age at onset between 20 and 40 years. However, VCD has been seen in very young children and in adults as old as 83, and its diagnosis in the pediatric population is increasing.¹⁸

The patient may present with complaints of atypical chest pain, throat tightness, stridor, choking, difficult vocalization, cough and sometimes dysphagia, GERD, or rhinosinusitis (see Table 1). These signs and symptoms may occur without provocation, or patients may relate a history of triggers such as anxiety, irritant exposure, or exercise. In fact, about 14% of VCD is associated with exercise, particularly in young female athletes who experience shortness of breath and even stridor with exercise.¹⁹

A characteristic finding on physical examination is inspiratory stridor, along with respiratory distress.²⁰ The stridor is best auscultated not over the anterior chest wall but over the tracheal area of the anterior neck.

Continue for differential diagnosis >>

DIFFERENTIAL DIAGNOSIS
Distinguishing VCD from other disorders can be challenging. Differential diagnosis should include
• Non–vocal cord adduction disorders, such as thyroid goiter, upper airway hemorrhage, caustic ingestion, neoplastic disorders, rheumatoid cricoarytenoid arthritis, pharyngeal abscess, angioedema, pulmonary embolus²¹
• Anatomic defects (eg, laryngomalacia, subglottic stenosis)
• Tracheal masses (eg, enlarged thyroid gland)
• Vocal cord polyps
• Laryngospasm
• Vocal cord paresis
• Neurologic causes (eg, brain stem compression, severe cortical injury, nuclear or lower motor neuron injury, movement disorders)
• Nonorganic causes (eg, factitious symptoms or malingering; conversion disorder)²²
• Reactive airway disease.
Some disorders are easier to distinguish from VCD than others. For example, although laryngospasm may produce similar symptoms, episodes are brief, lasting seconds to minutes; VCD episodes may last hours to days.

Asthma
Even the most astute clinician will be unable to obtain adequate information from the patient history to differentiate VCD from asthma. There is a significant overlap of symptoms—shortness of breath, cough, wheezing—and frequently, the diseases coexist. History is often negative for chest pain, but it is common for patients with VCD, when asked to describe their symptoms, to report chest tightness. The clinician therefore needs to ask the patient to point to where the tightness is felt—in the chest or in the neck over the laryngeal area—to distinguish the source.

Asthma symptoms usually increase over a few hours, days, or weeks but respond to medications that open the airway and reduce inflammation (inhaled β-agonists and corticosteroids). VCD symptoms usually occur or decrease suddenly and do not respond well to traditional asthma treatments.

Other differences between asthma and VCD symptoms include voice changes and time of day when symptoms occur. The person with VCD will experience voice changes, such as hoarseness, as well as prolonged coughing episodes. Patients with asthma may awaken at night because of breathlessness, while most patients with VCD experience symptoms only during the day.

The diagnosis is generally confirmed if VCD is seen on direct laryngoscopic visualization during a symptomatic episode. In terms of adduction, the anterior cords will appear normal, but the posterior portion of the cords will display the classic “glottis chink” (see Figure 2).⁹

If the diagnosis is in question, videostroboscopy, a technique that provides a magnified slow-motion view of vocal cord vibration, can help identify or exclude pathologic conditions of the vocal cords.²³

Convincing the patient of the validity of the diagnosis may be problematic if the patient has been previously diagnosed with and treated for another condition. The diagnosis should be explained and the patient counseled what appropriate care for VCD entails (see discussion under “Patient education and self-care”).

TREATMENT
Acute episode
During an acute VCD episode, offering the patient calm reassurance can be effective in resolving the episode. Simple breathing guidance may also be beneficial; instructing the patient to breathe rapidly and shallowly (ie, pant) can result in immediate resolution of symptoms.²⁴ The patient can be advised to utilize other techniques, such as diaphragmatic breathing, breathing through the nose, breathing through a straw, pursed-lip breathing, and exhaling with a hissing sound.²⁵

Long-term management
Although various strategies are employed in the management of VCD, well-designed studies on which to base treatment decisions have not been performed. Of course, control and management of possible underlying triggers or disorders should be implemented. Because etiology is rarely known, treatment for VCD is generally empiric.

Evidence does exist, however, to suggest that voice therapy, the treatment of choice for muscle tension dysphonia, is also effective for VCD. Speech therapy with specific voice and breathing exercises can enable the patient to manage the condition, thereby reducing ED visits, hospitalizations, and treatment costs.²⁶

Patient education and self-care
Patient education is a critical component of VCD management. The clinician should explain the functions of the larynx to the patient, including the normal functioning of the vocal cords during respiration, speaking, swallowing, coughing, throat clearing, and breath holding. It may also enhance patients’ understanding of VCD to view their diagnostic laryngoscopy or videostroboscopy films.²¹

The patient should be advised to rest the voice, hydrate, utilize sialagogues (lozenges, gum) to stimulate salivation, reduce exposure to triggers when possible, and decrease stress. She should be encouraged to track VCD triggers by documenting what she is doing, where, and when, at the time of a VCD episode.

Two exercises—“paused breathing” and “belly breathing”—can be used by patients to learn how to relax the vocal cords (see “Patient Handout”). Patients should practice these exercises three times a day so that they can be easily recalled and performed during VCD episodes.

Continue for outcomes >>

OUTCOMES
Little is known about long-term outcomes for patients with VCD. The current literature consists of poorly described and conflicting case reports and results of small trials. Although documentation is lacking, the authors agree that, by educating the patient about the diagnosis, teaching effective VCD management strategies, and referring patients for voice therapy, clinicians can help patients achieve signicant improvement. Further investigation is needed to enhance our knowledge of the causes of VCD and to research additional diagnostic modalities and treatments.²

CASE PATIENT
After diagnosing VCD, the clinician explained the normal functioning of the vocal cords and how certain factors may cause them to close during inspiration. The patient then understood why bronchodilator therapy had failed to relieve her symptoms. She was counseled to continue her inhaled nasal steroid and proton pump inhibitor for her perennial nonallergic rhinitis and GERD, respectively, because these conditions may trigger her VCD, and to take steps to manage her stress. She learned breathing techniques to alleviate acute episodes of VCD and was informed of the option of voice therapy with a speech therapist if needed.

At six-week follow-up, the patient reported that she was complying with her medication regimen, had made an effort to relax more, and had experienced no acute attacks of VCD since her last visit.

CONCLUSION
Patients with symptoms suggestive of VCD require a thorough evaluation, including laryngoscopic examination, to ensure accurate diagnosis and avoid a too-common misdiagnosis. Primary care clinicians should know about VCD and, if not trained in the performance of flexible laryngoscopy, should refer the symptomatic patient to a specialist for appropriate work-up.

CE/CME No: CR-1412

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Discuss the evolution in thinking about the pathogenesis of and treatment for vocal cord dysfunction (VCD).
• Describe the three primary functions of the healthy vocal cords.
• List the conditions or factors that may trigger VCD.
• Explain how to differentiate VCD from asthma.
• Develop a treatment plan for VCD that addresses both patient-specific VCD triggers and management of symptomatic episodes.

FACULTY
Linda S. MacConnell is an Assistant Professor in the Department of Physician Assistant Studies and Randy D. Danielsen is a Professor and Dean at the Arizona School of Health Sciences, AT Still University, Mesa. Ms. MacConnell is also a clinical PA affiliated with Enticare, an otolaryngology practice in Chandler, Arizona. Susan Symington is a clinical PA with the Arizona Asthma & Allergy Institute, with which Dr. Danielsen is also affiliated.
Linda MacConnell and Randy Danielsen have no significant financial relationships to disclose. Susan Symington is a member of the speaker’s bureau for Teva Respiratory and Thermo Fisher Scientific, Inc.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of December 2014.

Article begins on next page >>

The symptoms of vocal cord dysfunction (VCD) can be mistaken for those
of asthma or other respiratory illnesses. As a result, VCD is often misdiagnosed,
leading to unnecessary, ineffective, costly, or even dangerous treatment. Here are
the facts that will enable you to avoid making an erroneous diagnosis, choosing
potentially harmful treatment, and delaying effective treatment.

A 33-year-old oncology nurse, JD, had moved from Seattle to Phoenix about six months earlier for a job opportunity. Shortly after starting her new job, she had developed intermittent dyspnea on exertion, with a cough lasting several minutes at a time, along with a sensation of heaviness over the larynx and a choking sensation. These symptoms were precipitated by gastroesophageal reflux disease (GERD), postnasal drainage, stress, and significant environmental change (ie, Seattle to Phoenix). She noticed that, since moving to Phoenix, she frequently cleared her throat but denied any hoarseness, dysphagia, chest tightness, chest pain, or wheezing. She noted nasal congestion and clear nasal discharge on exposure to inhaled irritants (eg, woodstove smoke) and strong fragrances (eg, perfume or cologne).

On physical examination, the patient was alert, oriented, and in no acute distress. She was coughing intermittently but was able to speak in complete sentences. No stridor or dyspnea was noted, either on exertion (jogging in place) or at rest.

HEENT examination was normal, with no scalp lesions or tenderness; face, symmetric; light reflex, symmetric; conjunctivae, clear; sclera white, without lesions or redness; pupils, equal, reactive to light and accommodation; tympanic membranes and canals, clear with intact landmarks; no nasal deformities; nasal mucosa, mildly erythematous with mild engorgement of the turbinates; no nasal polyps seen; nasal septum midline without perforation; no sinus tenderness on percussion; pharynx, clear without exudate; uvula rises on phonation; and oral mucosa and gingivae, pink without lesions. Neck was supple without masses or thyromegaly, and trachea was midline. Lungs were clear to auscultation with normal respiratory movement and no accessory muscle use, with normal anteroposterior diameter. Heart examination revealed regular rate and rhythm, without murmur, clicks, or gallops.

Examination of the skin was normal, without rashes, hives, swelling, petechiae, or significant ecchymosis. There was no palpable cervical, supraclavicular, or axillary adenopathy.

Results of laboratory studies included a normal complete blood count with differential and a normal IgE level of 46.3 IU/mL. Spirometry testing revealed normal values without obstruction; however, there was a flattening of the inspiratory flow loop, with no reversibility after bronchodilator, which was highly suggestive of vocal cord dysfunction (VCD). Perennial nonallergic rhinitis (formerly called vasomotor rhinitis) was confirmed because the patient experienced fewer symptoms to perfume after nasal corticosteroid use. The patient’s GERD was generally well controlled with esomeprazole but was likely a contributing factor to her vocal cord symptoms.

On laryngoscopy, abnormal vocal cord movement toward the midline during both inspiration and expiration was visualized, confirming the diagnosis of VCD.

BACKGROUND
VCD is a partial upper airway obstruction caused by paradoxical adduction (medial movement) of the vocal cords.¹ Although it is primarily associated with inspiration, it sometimes manifests during expiration as well.

The true incidence of VCD is uncertain; different studies have found incidence rates varying from 2% to 27%, with higher rates in patients with asthma.^1,2 However, highlighting the risk for misdiagnosis, some 10% of patients evaluated for asthma unresponsive to aggressive treatment were found, in fact, to have VCD alone.²

Similarly, although VCD is generally more common in women than in men, the reported female-to-male ratio has varied from 2:1 to 4:1.^1,2,4 Some reports suggest that VCD is seen more frequently in younger women, with average ages at diagnosis of 14.5 in adolescents and 33 in adults.^2,3 Others identify a broader age range, with most patients older than 50.⁴

Historically, VCD has been known by a variety of names and has been observed clinically since 1842. In that year, Dunglison referred to it as hysteric croup, describing a disorder of the laryngeal muscles brought on by “hysteria.”⁵ Later, Mackenzie was able to visualize adduction of the vocal cords during inspiration in patients with stridor by using a laryngoscope.⁶ Osler demonstrated his understanding of the condition in 1902, stating, “Spasm of muscles may occur with violent inspiratory effort and great distress, and may even lead to cyanosis. Extraordinary cries may be produced either inspiratory or expiratory.”⁷

More recently, in 1974, Patterson et al reported finding laryngoscopic evidence of VCD, which they termed Munchausen’s stridor.⁸ They used this descriptor to report on the case of a young woman with 15 hospital admissions for this condition. At the time, the etiology of the condition was believed to be largely psychologic, and its evaluation was consigned to psychiatrists and other mental health practitioners.

As laryngoscopy became more widely available in the 1970s and 1980s, diagnosis of VCD increased, although the condition remains underrecognized.⁹ Ibrahim et al suggest that primary care clinicians may not be as aware of VCD as they should be and may not consider laryngoscopy for possible VCD in patients whose asthma is poorly controlled.²

Disagreement persists with regard to the preferred name for the condition. Because numerous disorders involve abnormal vocal cord function, Christopher proposed moving away from the broad term VCD and toward a more descriptive term: paradoxical vocal fold motion (PVFM) disorder.¹⁰ Interestingly, use of the two terms seems to be divided along specialty lines: VCD is preferred by allergy, pulmonology, and mental health specialists, while PVFM is favored by otolaryngology specialists and speech-language pathologists.¹¹

Further complicating awareness and recognition of VCD is its longstanding reputation as a psychologic disorder. In fact, the paradigm has shifted away from defining VCD as a purely psychopathologic entity to the identification of numerous functional etiologies for the disorder. This, however, has resulted in many new terms to describe the condition, including nonorganic upper airway obstruction, pseudoasthma, irritable larynx syndrome, factitious asthma, spasmodic croup, functional upper airway obstruction, episodic laryngeal dyskinesia, functional laryngeal obstruction, functional laryngeal stridor, and episodic paroxysmal laryngospasm.¹

Regardless of its name, an understanding of VCD is essential for both primary care and specialty clinicians because of its frequent misdiagnosis as asthma, allergies, or severe upper airway obstruction. When it is misdiagnosed as asthma, aggressive asthma treatments—to which VCD does not respond—may be prescribed, including high-dose inhaled and systemic corticosteroids and bronchodilators. Patients may experience multiple emergency department (ED) visits and hospitalizations and, in some cases, may be subjected to tracheostomies and intubation.

Continue for vocal cord physiology and functions >>

VOCAL CORD PHYSIOLOGY AND FUNCTIONS
The vocal cords are located within the larynx. Abduction, or opening, of the cords is controlled by the posterior cricoarytenoid muscle; adduction, or closing, occurs via contraction of the lateral cricoarytenoid muscle. These muscles are innervated by the recurrent laryngeal nerve to control the width of the space—the rima glottidis—between the cords. During inspiration, the glottis opens; during expiration, it narrows but remains open.¹²

The vocal cords are involved in three main functions: protection of the airway, respiration, and phonation (vocal production). These functions are at least partially controlled involuntarily by brain stem reflexes; however, only airway protection—the most important of these functions—is reflexive and involuntary.¹² Respiration may be controlled voluntarily, and phonation is primarily voluntary. Closure of the vocal cords is under the control of the laryngeal nerve branches of the vagal nerve.^12,13

The vocal cords normally abduct during inspiration to allow air to pass through them into the trachea and the lungs. Sniffing, puffing, snuffling, and panting also cause the vocal cords to abduct. The vocal cords adduct with phonation (talking, singing), coughing, clearing the throat, performing the Valsalva maneuver, and swallowing. During expiration, 10% to 40% adduction is considered normal.¹⁴

VOCAL CORD DYSFUNCTION
Pathogenesis and etiology
VCD is a nonspecific term, and a number of factors may be involved in its development.¹⁵ Although the precise cause of VCD is unknown, it is believed to result from laryngeal hyperresponsiveness. This exaggerated responsiveness may be prompted by irritant and nonirritant triggers of the sensory receptors in the larynx, trachea, and large airways that mediate cough and glottis closure reflexes.¹⁶

VCD may be among a group of airway disorders triggered by occupational exposures, including irritants and psychologic stressors. For example, occupationally triggered VCD was diagnosed in rescue, recovery, and cleanup workers at the World Trade Center disaster site.⁴

A history of childhood sexual abuse has also been associated by some researchers with the development of VCD. For example, Freedman et al reported that, of 47 patients with VCD, 14 identified such a history and five were suspected of having been sexually abused as children.¹⁷

Paradoxical movement of the vocal cords causes them to close when they should open. (Click here for a video on normal and abnormal vocal cord movement.) VCD generally occurs during inspiration, causing obstruction of the incoming air through the larynx. Symptoms of VCD frequently include dyspnea, coughing, wheezing, hoarseness, and tightness or pain in the throat.

Examination of the flow-volume loops recorded when a patient experiences “wheezing” during spirometry testing reveals a flattened inspiratory loop, indicating a decrease of airflow into the lungs (see Figure 1).^13,16 “Wheezing” is actually a misnomer in this situation because the term typically refers to sounds that occur during expiration.

Triggers
Physiologic, psychologic, and neurologic factors may all contribute to VCD.^1,15 Conditions that can trigger VCD include
• Asthma
• Postnasal drip
• Recent upper respiratory illness (URI)
• Talking, singing
• Exercise
• Cough
• Voice strain
• Stress, anxiety, tension, elevated emotions
• Common irritants (eg, strong smells)
• Airborne irritants
• Rhinosinusitis
• GERD
• Use of certain medications
Identification of a particular patient’s triggers is key to successful management of VCD.

PATIENT PRESENTATION
Although there is no “typical” patient with VCD, the condition occurs more frequently in women, with the most common age at onset between 20 and 40 years. However, VCD has been seen in very young children and in adults as old as 83, and its diagnosis in the pediatric population is increasing.¹⁸

The patient may present with complaints of atypical chest pain, throat tightness, stridor, choking, difficult vocalization, cough and sometimes dysphagia, GERD, or rhinosinusitis (see Table 1). These signs and symptoms may occur without provocation, or patients may relate a history of triggers such as anxiety, irritant exposure, or exercise. In fact, about 14% of VCD is associated with exercise, particularly in young female athletes who experience shortness of breath and even stridor with exercise.¹⁹

A characteristic finding on physical examination is inspiratory stridor, along with respiratory distress.²⁰ The stridor is best auscultated not over the anterior chest wall but over the tracheal area of the anterior neck.

Continue for differential diagnosis >>

DIFFERENTIAL DIAGNOSIS
Distinguishing VCD from other disorders can be challenging. Differential diagnosis should include
• Non–vocal cord adduction disorders, such as thyroid goiter, upper airway hemorrhage, caustic ingestion, neoplastic disorders, rheumatoid cricoarytenoid arthritis, pharyngeal abscess, angioedema, pulmonary embolus²¹
• Anatomic defects (eg, laryngomalacia, subglottic stenosis)
• Tracheal masses (eg, enlarged thyroid gland)
• Vocal cord polyps
• Laryngospasm
• Vocal cord paresis
• Neurologic causes (eg, brain stem compression, severe cortical injury, nuclear or lower motor neuron injury, movement disorders)
• Nonorganic causes (eg, factitious symptoms or malingering; conversion disorder)²²
• Reactive airway disease.
Some disorders are easier to distinguish from VCD than others. For example, although laryngospasm may produce similar symptoms, episodes are brief, lasting seconds to minutes; VCD episodes may last hours to days.

Asthma
Even the most astute clinician will be unable to obtain adequate information from the patient history to differentiate VCD from asthma. There is a significant overlap of symptoms—shortness of breath, cough, wheezing—and frequently, the diseases coexist. History is often negative for chest pain, but it is common for patients with VCD, when asked to describe their symptoms, to report chest tightness. The clinician therefore needs to ask the patient to point to where the tightness is felt—in the chest or in the neck over the laryngeal area—to distinguish the source.

Asthma symptoms usually increase over a few hours, days, or weeks but respond to medications that open the airway and reduce inflammation (inhaled β-agonists and corticosteroids). VCD symptoms usually occur or decrease suddenly and do not respond well to traditional asthma treatments.

Other differences between asthma and VCD symptoms include voice changes and time of day when symptoms occur. The person with VCD will experience voice changes, such as hoarseness, as well as prolonged coughing episodes. Patients with asthma may awaken at night because of breathlessness, while most patients with VCD experience symptoms only during the day.

The diagnosis is generally confirmed if VCD is seen on direct laryngoscopic visualization during a symptomatic episode. In terms of adduction, the anterior cords will appear normal, but the posterior portion of the cords will display the classic “glottis chink” (see Figure 2).⁹

If the diagnosis is in question, videostroboscopy, a technique that provides a magnified slow-motion view of vocal cord vibration, can help identify or exclude pathologic conditions of the vocal cords.²³

Convincing the patient of the validity of the diagnosis may be problematic if the patient has been previously diagnosed with and treated for another condition. The diagnosis should be explained and the patient counseled what appropriate care for VCD entails (see discussion under “Patient education and self-care”).

TREATMENT
Acute episode
During an acute VCD episode, offering the patient calm reassurance can be effective in resolving the episode. Simple breathing guidance may also be beneficial; instructing the patient to breathe rapidly and shallowly (ie, pant) can result in immediate resolution of symptoms.²⁴ The patient can be advised to utilize other techniques, such as diaphragmatic breathing, breathing through the nose, breathing through a straw, pursed-lip breathing, and exhaling with a hissing sound.²⁵

Long-term management
Although various strategies are employed in the management of VCD, well-designed studies on which to base treatment decisions have not been performed. Of course, control and management of possible underlying triggers or disorders should be implemented. Because etiology is rarely known, treatment for VCD is generally empiric.

Evidence does exist, however, to suggest that voice therapy, the treatment of choice for muscle tension dysphonia, is also effective for VCD. Speech therapy with specific voice and breathing exercises can enable the patient to manage the condition, thereby reducing ED visits, hospitalizations, and treatment costs.²⁶

Patient education and self-care
Patient education is a critical component of VCD management. The clinician should explain the functions of the larynx to the patient, including the normal functioning of the vocal cords during respiration, speaking, swallowing, coughing, throat clearing, and breath holding. It may also enhance patients’ understanding of VCD to view their diagnostic laryngoscopy or videostroboscopy films.²¹

The patient should be advised to rest the voice, hydrate, utilize sialagogues (lozenges, gum) to stimulate salivation, reduce exposure to triggers when possible, and decrease stress. She should be encouraged to track VCD triggers by documenting what she is doing, where, and when, at the time of a VCD episode.

Two exercises—“paused breathing” and “belly breathing”—can be used by patients to learn how to relax the vocal cords (see “Patient Handout”). Patients should practice these exercises three times a day so that they can be easily recalled and performed during VCD episodes.

Continue for outcomes >>

OUTCOMES
Little is known about long-term outcomes for patients with VCD. The current literature consists of poorly described and conflicting case reports and results of small trials. Although documentation is lacking, the authors agree that, by educating the patient about the diagnosis, teaching effective VCD management strategies, and referring patients for voice therapy, clinicians can help patients achieve signicant improvement. Further investigation is needed to enhance our knowledge of the causes of VCD and to research additional diagnostic modalities and treatments.²

CASE PATIENT
After diagnosing VCD, the clinician explained the normal functioning of the vocal cords and how certain factors may cause them to close during inspiration. The patient then understood why bronchodilator therapy had failed to relieve her symptoms. She was counseled to continue her inhaled nasal steroid and proton pump inhibitor for her perennial nonallergic rhinitis and GERD, respectively, because these conditions may trigger her VCD, and to take steps to manage her stress. She learned breathing techniques to alleviate acute episodes of VCD and was informed of the option of voice therapy with a speech therapist if needed.

At six-week follow-up, the patient reported that she was complying with her medication regimen, had made an effort to relax more, and had experienced no acute attacks of VCD since her last visit.

CONCLUSION
Patients with symptoms suggestive of VCD require a thorough evaluation, including laryngoscopic examination, to ensure accurate diagnosis and avoid a too-common misdiagnosis. Primary care clinicians should know about VCD and, if not trained in the performance of flexible laryngoscopy, should refer the symptomatic patient to a specialist for appropriate work-up.

VANCOUVER, B.C. – The “shotgun” style of skin prick testing in children and adolescents with suspected IgE-mediated food allergy shows sensitization, but not necessarily allergy, according to Dr. James Bergman.

A positive skin test measures the presence of a specific IgE antibody, which does not necessarily equate to an allergy. Consequently, children may have multiple positive skin prick tests yet clinically tolerate the tested food, he said. “Sensitization is just the presence of a specific IgE to a food. Allergy is sensitization plus signs or symptoms upon exposure to the food.”

Dr. Bergman, who also holds a faculty position in the department of dermatology and skin science at the University of British Columbia, said the practice of shotgun skin prick testing can lead to unnecessary avoidance of specific foods. One group of researchers conducted oral food challenge tests in 125 children aged 1-9 years with a diagnosis of food allergy based on IgE tests. Nearly all of them (93%) had no reactivity when challenged with the suspect food (J. Peds. 2011; 158[4]:578-83). “Ninety-three percent of the children would have been avoiding their ‘allergic foods’ perhaps indefinitely,” said Dr. Bergman, who was not involved with the study.

“The general rule is, if you’re not having clinical symptoms that suggest an IgE-mediated reaction, then don’t test,” Dr. Bergman, a dermatologist who practices in Vancouver, said at the annual meeting of the Pacific Dermatologic Association.

“I explain to parents that if they want to test for a food in the situation where there is no IgE-mediated reaction, then it can be done, but there is a significant risk of a false positive or ‘fake allergy,’ ” he said. “In this situation the only way of knowing for sure whether it is an allergy is to undertake a formal oral food challenge, which is the (highest) standard for diagnosing food allergy.”

Telltale symptoms of an IgE-mediated food allergy include hives, vomiting, diarrhea, breathing problems, and change in level of consciousness. “These symptoms typically occur within minutes of ingestion, sometimes within 30 minutes and rarely up to 2 hours,” Dr. Bergman said. “If it’s beyond 2 hours, it’s unlikely to be IgE mediated.”

“If someone has a true food allergy, advise them to avoid the culprit food, give them an epinephrine injector, and refer them to an allergist for testing, education, and follow-up,” he advised.

Food allergies affect 6%-8% of pediatric patients, yet 35%- 90% of families self-report food allergies depending on the population studied. Milk, egg, wheat, peanuts, nuts, soy, and seafood account for 90% of food allergens. Most children outgrow allergy to milk, egg, wheat, and soy, while few outgrow allergy to peanuts, nuts, fish, and shellfish.

Most patients and many physicians believe that eczema is caused by food allergies. In fact, only a small minority of patients have food allergies that directly cause eczema. “Eczema could occur secondary to scratching induced by an urticarial food reaction or by a primary irritant reaction, but food directly causing isolated eczema is rare,” Dr. Bergman said. “The belief that food allergies directly cause eczema is completely understandable given that eczema patients do have an increased rate of allergies, the cyclic pattern of eczema, and the parent’s desire to find a cause for the child’s rash. Eczema’s cyclic nature can easily lead to a specific food being implicated due to recall bias. The parent will remember the flares that occurred with exposure to the specific food, while not recalling the times when the food was tolerated or the flares that were not associated with the food.”

If a parent is worried about a food causing eczema and there are no IgE mediated symptoms, then instead of testing he will often recommend that the family keep a formal food symptom diary while they are intermittently ingesting the food of concern. “The vast majority of parents will see no consistent direct correlation with the food and they can feel comfortable with ongoing future ingestion,” he said.

Some clinicians are offering oral immune therapy to patients with IgE-mediated food allergy. Dr. Bergman characterized such practice as “risky” at this point in time. “It’s like the traditional allergy shots you’d get for your pollen allergy, except it’s done orally,” he explained. “Research is being done in this area by introducing small amounts [of the allergen], in an attempt to induce tolerance. The results are encouraging, but the problem is that patients can have bad reactions. We also don’t know how well or for how long it will work. At this point, while promising, the field is not yet ready for prime time.”

He also said there is no current evidence supporting IgG testing, Vega testing, or muscle strength testing in the investigation of suspected IgE-mediated food allergy. “What I tell patients is that if any of these tests identifies something, it probably identifies something that’s mild and very temporary, because in my experience patients with positive IgG tests are usually told to avoid the food for 1-4 months and then to reintroduce that food in a rotation basis. Avoidance of food allergens based on this type of testing is not necessary. However, for patients who still wish to practice short term avoidance of the food then this is fine provided the diet does not compromise nutrition.”

Dr. Bergman reported having no financial disclosures.

[email protected]

On Twitter @dougbrunk

VANCOUVER, B.C. – The “shotgun” style of skin prick testing in children and adolescents with suspected IgE-mediated food allergy shows sensitization, but not necessarily allergy, according to Dr. James Bergman.

A positive skin test measures the presence of a specific IgE antibody, which does not necessarily equate to an allergy. Consequently, children may have multiple positive skin prick tests yet clinically tolerate the tested food, he said. “Sensitization is just the presence of a specific IgE to a food. Allergy is sensitization plus signs or symptoms upon exposure to the food.”

Dr. Bergman, who also holds a faculty position in the department of dermatology and skin science at the University of British Columbia, said the practice of shotgun skin prick testing can lead to unnecessary avoidance of specific foods. One group of researchers conducted oral food challenge tests in 125 children aged 1-9 years with a diagnosis of food allergy based on IgE tests. Nearly all of them (93%) had no reactivity when challenged with the suspect food (J. Peds. 2011; 158[4]:578-83). “Ninety-three percent of the children would have been avoiding their ‘allergic foods’ perhaps indefinitely,” said Dr. Bergman, who was not involved with the study.

“The general rule is, if you’re not having clinical symptoms that suggest an IgE-mediated reaction, then don’t test,” Dr. Bergman, a dermatologist who practices in Vancouver, said at the annual meeting of the Pacific Dermatologic Association.

“I explain to parents that if they want to test for a food in the situation where there is no IgE-mediated reaction, then it can be done, but there is a significant risk of a false positive or ‘fake allergy,’ ” he said. “In this situation the only way of knowing for sure whether it is an allergy is to undertake a formal oral food challenge, which is the (highest) standard for diagnosing food allergy.”

Telltale symptoms of an IgE-mediated food allergy include hives, vomiting, diarrhea, breathing problems, and change in level of consciousness. “These symptoms typically occur within minutes of ingestion, sometimes within 30 minutes and rarely up to 2 hours,” Dr. Bergman said. “If it’s beyond 2 hours, it’s unlikely to be IgE mediated.”

“If someone has a true food allergy, advise them to avoid the culprit food, give them an epinephrine injector, and refer them to an allergist for testing, education, and follow-up,” he advised.

Food allergies affect 6%-8% of pediatric patients, yet 35%- 90% of families self-report food allergies depending on the population studied. Milk, egg, wheat, peanuts, nuts, soy, and seafood account for 90% of food allergens. Most children outgrow allergy to milk, egg, wheat, and soy, while few outgrow allergy to peanuts, nuts, fish, and shellfish.

Most patients and many physicians believe that eczema is caused by food allergies. In fact, only a small minority of patients have food allergies that directly cause eczema. “Eczema could occur secondary to scratching induced by an urticarial food reaction or by a primary irritant reaction, but food directly causing isolated eczema is rare,” Dr. Bergman said. “The belief that food allergies directly cause eczema is completely understandable given that eczema patients do have an increased rate of allergies, the cyclic pattern of eczema, and the parent’s desire to find a cause for the child’s rash. Eczema’s cyclic nature can easily lead to a specific food being implicated due to recall bias. The parent will remember the flares that occurred with exposure to the specific food, while not recalling the times when the food was tolerated or the flares that were not associated with the food.”

If a parent is worried about a food causing eczema and there are no IgE mediated symptoms, then instead of testing he will often recommend that the family keep a formal food symptom diary while they are intermittently ingesting the food of concern. “The vast majority of parents will see no consistent direct correlation with the food and they can feel comfortable with ongoing future ingestion,” he said.

Some clinicians are offering oral immune therapy to patients with IgE-mediated food allergy. Dr. Bergman characterized such practice as “risky” at this point in time. “It’s like the traditional allergy shots you’d get for your pollen allergy, except it’s done orally,” he explained. “Research is being done in this area by introducing small amounts [of the allergen], in an attempt to induce tolerance. The results are encouraging, but the problem is that patients can have bad reactions. We also don’t know how well or for how long it will work. At this point, while promising, the field is not yet ready for prime time.”

He also said there is no current evidence supporting IgG testing, Vega testing, or muscle strength testing in the investigation of suspected IgE-mediated food allergy. “What I tell patients is that if any of these tests identifies something, it probably identifies something that’s mild and very temporary, because in my experience patients with positive IgG tests are usually told to avoid the food for 1-4 months and then to reintroduce that food in a rotation basis. Avoidance of food allergens based on this type of testing is not necessary. However, for patients who still wish to practice short term avoidance of the food then this is fine provided the diet does not compromise nutrition.”

Dr. Bergman reported having no financial disclosures.

[email protected]

On Twitter @dougbrunk

VANCOUVER, B.C. – The “shotgun” style of skin prick testing in children and adolescents with suspected IgE-mediated food allergy shows sensitization, but not necessarily allergy, according to Dr. James Bergman.

A positive skin test measures the presence of a specific IgE antibody, which does not necessarily equate to an allergy. Consequently, children may have multiple positive skin prick tests yet clinically tolerate the tested food, he said. “Sensitization is just the presence of a specific IgE to a food. Allergy is sensitization plus signs or symptoms upon exposure to the food.”

Dr. Bergman, who also holds a faculty position in the department of dermatology and skin science at the University of British Columbia, said the practice of shotgun skin prick testing can lead to unnecessary avoidance of specific foods. One group of researchers conducted oral food challenge tests in 125 children aged 1-9 years with a diagnosis of food allergy based on IgE tests. Nearly all of them (93%) had no reactivity when challenged with the suspect food (J. Peds. 2011; 158[4]:578-83). “Ninety-three percent of the children would have been avoiding their ‘allergic foods’ perhaps indefinitely,” said Dr. Bergman, who was not involved with the study.

“The general rule is, if you’re not having clinical symptoms that suggest an IgE-mediated reaction, then don’t test,” Dr. Bergman, a dermatologist who practices in Vancouver, said at the annual meeting of the Pacific Dermatologic Association.

“I explain to parents that if they want to test for a food in the situation where there is no IgE-mediated reaction, then it can be done, but there is a significant risk of a false positive or ‘fake allergy,’ ” he said. “In this situation the only way of knowing for sure whether it is an allergy is to undertake a formal oral food challenge, which is the (highest) standard for diagnosing food allergy.”

Telltale symptoms of an IgE-mediated food allergy include hives, vomiting, diarrhea, breathing problems, and change in level of consciousness. “These symptoms typically occur within minutes of ingestion, sometimes within 30 minutes and rarely up to 2 hours,” Dr. Bergman said. “If it’s beyond 2 hours, it’s unlikely to be IgE mediated.”

“If someone has a true food allergy, advise them to avoid the culprit food, give them an epinephrine injector, and refer them to an allergist for testing, education, and follow-up,” he advised.

Food allergies affect 6%-8% of pediatric patients, yet 35%- 90% of families self-report food allergies depending on the population studied. Milk, egg, wheat, peanuts, nuts, soy, and seafood account for 90% of food allergens. Most children outgrow allergy to milk, egg, wheat, and soy, while few outgrow allergy to peanuts, nuts, fish, and shellfish.

Most patients and many physicians believe that eczema is caused by food allergies. In fact, only a small minority of patients have food allergies that directly cause eczema. “Eczema could occur secondary to scratching induced by an urticarial food reaction or by a primary irritant reaction, but food directly causing isolated eczema is rare,” Dr. Bergman said. “The belief that food allergies directly cause eczema is completely understandable given that eczema patients do have an increased rate of allergies, the cyclic pattern of eczema, and the parent’s desire to find a cause for the child’s rash. Eczema’s cyclic nature can easily lead to a specific food being implicated due to recall bias. The parent will remember the flares that occurred with exposure to the specific food, while not recalling the times when the food was tolerated or the flares that were not associated with the food.”

If a parent is worried about a food causing eczema and there are no IgE mediated symptoms, then instead of testing he will often recommend that the family keep a formal food symptom diary while they are intermittently ingesting the food of concern. “The vast majority of parents will see no consistent direct correlation with the food and they can feel comfortable with ongoing future ingestion,” he said.

Some clinicians are offering oral immune therapy to patients with IgE-mediated food allergy. Dr. Bergman characterized such practice as “risky” at this point in time. “It’s like the traditional allergy shots you’d get for your pollen allergy, except it’s done orally,” he explained. “Research is being done in this area by introducing small amounts [of the allergen], in an attempt to induce tolerance. The results are encouraging, but the problem is that patients can have bad reactions. We also don’t know how well or for how long it will work. At this point, while promising, the field is not yet ready for prime time.”

He also said there is no current evidence supporting IgG testing, Vega testing, or muscle strength testing in the investigation of suspected IgE-mediated food allergy. “What I tell patients is that if any of these tests identifies something, it probably identifies something that’s mild and very temporary, because in my experience patients with positive IgG tests are usually told to avoid the food for 1-4 months and then to reintroduce that food in a rotation basis. Avoidance of food allergens based on this type of testing is not necessary. However, for patients who still wish to practice short term avoidance of the food then this is fine provided the diet does not compromise nutrition.”

Dr. Bergman reported having no financial disclosures.

[email protected]

On Twitter @dougbrunk