Pulmonary Health Hub

THE CASE

A 25-year-old man, who was an active duty US Navy sailor, went to his ship’s medical department complaining of a mild cough that he’d had for 2 days. He denied having any fevers, chills, night sweats, angina, or dyspnea. He said he hadn’t experienced any exertional fatigue or difficulty completing the rigorous physical tasks of his occupation as an engineman on the ship. The patient had no medical or surgical history of significance, and he wasn’t taking any medications or supplements.

On exam, he was not in acute distress and his vital signs were within normal limits. Auscultation revealed mild wheezing throughout the upper lung fields and loud heart sounds throughout his chest that were audible even with gentle contact of the stethoscope diaphragm. He had no discernible murmurs, rubs, or gallops.

In light of the unusually loud heart sounds heard on exam, we performed an electrocardiogram. The EKG revealed a normal sinus rhythm, slight right axis deviation indicated by tall R-waves in V1 (also suggestive of right ventricular hypertrophy), an incomplete right bundle branch block, and a crochetage sign (a notch in the R-waves of the inferior leads).¹ A chest x-ray (FIGURE 1) revealed a normal-sized heart and dilated pulmonary vasculature suggestive of pulmonary hypertension.

THE DIAGNOSIS

To further evaluate the cardiopulmonary findings, ultrasound studies (transthoracic and transesophageal echocardiography) were performed. These demonstrated a very large secundum-type atrial septal defect (ASD), measuring at its largest point about 30 × 48 mm (FIGURE 2 and FIGURE 3C). Doppler flow analysis and a bubble study (VIDEOS 1 and 2) demonstrated significant shunting across the ASD. Gated cardiac computed tomography (CT) was also used to characterize the ASD (FIGURE 3). It revealed that the superior and posterior rims of the ASD were essentially absent and that the right atrium and ventricle were severely enlarged, while the left chambers were normal in size and function with an ejection fraction >55%. The notching of the R-waves of the inferior leads, seen in our patient’s EKG, is typically seen with large ASDs.^1,2

DISCUSSION

ASDs are typically uncovered on exam via auscultation of heart sounds, which might reveal a split of the second heart sound (S2) and diastolic murmurs. ASDs are typically classified by size, and their management depends on this factor, along with the patient’s age and symptoms. In children with small defects (<6 mm), treatment usually consists of conservative observation, as more than half of these ASDs will spontaneously close.³ But, as children age, they are more likely to engage in exertional activity (work, recreational sports) and an unrepaired ASD may yield symptoms (angina, dyspnea, fatigue, other cardiopulmonary strain). With such symptoms and when closure is not spontaneously achieved by adolescence or adulthood, an invasive approach is often necessary to correct the defect.

ASD repair. Traditionally, repair has involved some form of open thoracotomy. More recently, several minimally invasive techniques have been developed. Catheter-based device closure, in which a catheter is percutaneously guided to the defect and a patch is deployed to seal the ASD, is a technique that has been shown to successfully correct large ASDs of up to 40 mm in size.⁴ Robotic procedures have also been developed to correct ASDs through much smaller incisions.⁵ Both of these techniques require a significant rim of residual septal tissue around the defect.

Individualized approach. Since our patient had a rather large ASD that did not have sufficient residual septal rim tissue, percutaneous and robotic approaches were not feasible. Instead, he required more invasive cardiothoracic surgery. In cases such as this, the exact technique and type of incision (sternotomy vs access through the lateral chest wall) depend on age, gender, and the presence of other comorbidities.⁶

Our patient. Because there was concern that any approach other than a median one might not afford enough space to fix an ASD of such considerable size, our patient underwent a median sternotomy by a pediatric cardiothoracic surgeon who specialized in these repairs (in children as well as young adults). During the procedure, the ASD was accessed and confirmed to be as large as predicted by diagnostic imaging. A surgical patch was sutured in place to correct the defect. There were no intra-operative or postop complications.

Four weeks later, the patient had a mild pericardial effusion that was managed medically with daily furosemide and aspirin. At his 8-week postop appointment, the fluid accumulation had resolved, and he was completely asymptomatic. The patient returned to full-time active duty in the US Navy.

THE TAKEAWAY

Adults with rather large ASDs can present in a relatively asymptomatic manner and report none of the classic complaints (angina, dyspnea, fatigue). They may even engage in heavy exertional activity with no difficulty. The underlying defect may be discovered incidentally on exam by noting a split of the S2 on auscultation. If pulmonary hypertension exists, the clinician may also note a loud S2. An exam that raises suspicion for an ASD can then be followed by tests that solidify the diagnosis. Surgery is usually necessary to correct an ASD in an adult who is symptomatic or exhibits significant cardiopulmonary strain.

THE CASE

A 25-year-old man, who was an active duty US Navy sailor, went to his ship’s medical department complaining of a mild cough that he’d had for 2 days. He denied having any fevers, chills, night sweats, angina, or dyspnea. He said he hadn’t experienced any exertional fatigue or difficulty completing the rigorous physical tasks of his occupation as an engineman on the ship. The patient had no medical or surgical history of significance, and he wasn’t taking any medications or supplements.

On exam, he was not in acute distress and his vital signs were within normal limits. Auscultation revealed mild wheezing throughout the upper lung fields and loud heart sounds throughout his chest that were audible even with gentle contact of the stethoscope diaphragm. He had no discernible murmurs, rubs, or gallops.

In light of the unusually loud heart sounds heard on exam, we performed an electrocardiogram. The EKG revealed a normal sinus rhythm, slight right axis deviation indicated by tall R-waves in V1 (also suggestive of right ventricular hypertrophy), an incomplete right bundle branch block, and a crochetage sign (a notch in the R-waves of the inferior leads).¹ A chest x-ray (FIGURE 1) revealed a normal-sized heart and dilated pulmonary vasculature suggestive of pulmonary hypertension.

THE DIAGNOSIS

To further evaluate the cardiopulmonary findings, ultrasound studies (transthoracic and transesophageal echocardiography) were performed. These demonstrated a very large secundum-type atrial septal defect (ASD), measuring at its largest point about 30 × 48 mm (FIGURE 2 and FIGURE 3C). Doppler flow analysis and a bubble study (VIDEOS 1 and 2) demonstrated significant shunting across the ASD. Gated cardiac computed tomography (CT) was also used to characterize the ASD (FIGURE 3). It revealed that the superior and posterior rims of the ASD were essentially absent and that the right atrium and ventricle were severely enlarged, while the left chambers were normal in size and function with an ejection fraction >55%. The notching of the R-waves of the inferior leads, seen in our patient’s EKG, is typically seen with large ASDs.^1,2

DISCUSSION

ASDs are typically uncovered on exam via auscultation of heart sounds, which might reveal a split of the second heart sound (S2) and diastolic murmurs. ASDs are typically classified by size, and their management depends on this factor, along with the patient’s age and symptoms. In children with small defects (<6 mm), treatment usually consists of conservative observation, as more than half of these ASDs will spontaneously close.³ But, as children age, they are more likely to engage in exertional activity (work, recreational sports) and an unrepaired ASD may yield symptoms (angina, dyspnea, fatigue, other cardiopulmonary strain). With such symptoms and when closure is not spontaneously achieved by adolescence or adulthood, an invasive approach is often necessary to correct the defect.

ASD repair. Traditionally, repair has involved some form of open thoracotomy. More recently, several minimally invasive techniques have been developed. Catheter-based device closure, in which a catheter is percutaneously guided to the defect and a patch is deployed to seal the ASD, is a technique that has been shown to successfully correct large ASDs of up to 40 mm in size.⁴ Robotic procedures have also been developed to correct ASDs through much smaller incisions.⁵ Both of these techniques require a significant rim of residual septal tissue around the defect.

Individualized approach. Since our patient had a rather large ASD that did not have sufficient residual septal rim tissue, percutaneous and robotic approaches were not feasible. Instead, he required more invasive cardiothoracic surgery. In cases such as this, the exact technique and type of incision (sternotomy vs access through the lateral chest wall) depend on age, gender, and the presence of other comorbidities.⁶

Our patient. Because there was concern that any approach other than a median one might not afford enough space to fix an ASD of such considerable size, our patient underwent a median sternotomy by a pediatric cardiothoracic surgeon who specialized in these repairs (in children as well as young adults). During the procedure, the ASD was accessed and confirmed to be as large as predicted by diagnostic imaging. A surgical patch was sutured in place to correct the defect. There were no intra-operative or postop complications.

Four weeks later, the patient had a mild pericardial effusion that was managed medically with daily furosemide and aspirin. At his 8-week postop appointment, the fluid accumulation had resolved, and he was completely asymptomatic. The patient returned to full-time active duty in the US Navy.

THE TAKEAWAY

Adults with rather large ASDs can present in a relatively asymptomatic manner and report none of the classic complaints (angina, dyspnea, fatigue). They may even engage in heavy exertional activity with no difficulty. The underlying defect may be discovered incidentally on exam by noting a split of the S2 on auscultation. If pulmonary hypertension exists, the clinician may also note a loud S2. An exam that raises suspicion for an ASD can then be followed by tests that solidify the diagnosis. Surgery is usually necessary to correct an ASD in an adult who is symptomatic or exhibits significant cardiopulmonary strain.

THE CASE

A 25-year-old man, who was an active duty US Navy sailor, went to his ship’s medical department complaining of a mild cough that he’d had for 2 days. He denied having any fevers, chills, night sweats, angina, or dyspnea. He said he hadn’t experienced any exertional fatigue or difficulty completing the rigorous physical tasks of his occupation as an engineman on the ship. The patient had no medical or surgical history of significance, and he wasn’t taking any medications or supplements.

On exam, he was not in acute distress and his vital signs were within normal limits. Auscultation revealed mild wheezing throughout the upper lung fields and loud heart sounds throughout his chest that were audible even with gentle contact of the stethoscope diaphragm. He had no discernible murmurs, rubs, or gallops.

In light of the unusually loud heart sounds heard on exam, we performed an electrocardiogram. The EKG revealed a normal sinus rhythm, slight right axis deviation indicated by tall R-waves in V1 (also suggestive of right ventricular hypertrophy), an incomplete right bundle branch block, and a crochetage sign (a notch in the R-waves of the inferior leads).¹ A chest x-ray (FIGURE 1) revealed a normal-sized heart and dilated pulmonary vasculature suggestive of pulmonary hypertension.

THE DIAGNOSIS

To further evaluate the cardiopulmonary findings, ultrasound studies (transthoracic and transesophageal echocardiography) were performed. These demonstrated a very large secundum-type atrial septal defect (ASD), measuring at its largest point about 30 × 48 mm (FIGURE 2 and FIGURE 3C). Doppler flow analysis and a bubble study (VIDEOS 1 and 2) demonstrated significant shunting across the ASD. Gated cardiac computed tomography (CT) was also used to characterize the ASD (FIGURE 3). It revealed that the superior and posterior rims of the ASD were essentially absent and that the right atrium and ventricle were severely enlarged, while the left chambers were normal in size and function with an ejection fraction >55%. The notching of the R-waves of the inferior leads, seen in our patient’s EKG, is typically seen with large ASDs.^1,2

DISCUSSION

ASDs are typically uncovered on exam via auscultation of heart sounds, which might reveal a split of the second heart sound (S2) and diastolic murmurs. ASDs are typically classified by size, and their management depends on this factor, along with the patient’s age and symptoms. In children with small defects (<6 mm), treatment usually consists of conservative observation, as more than half of these ASDs will spontaneously close.³ But, as children age, they are more likely to engage in exertional activity (work, recreational sports) and an unrepaired ASD may yield symptoms (angina, dyspnea, fatigue, other cardiopulmonary strain). With such symptoms and when closure is not spontaneously achieved by adolescence or adulthood, an invasive approach is often necessary to correct the defect.

ASD repair. Traditionally, repair has involved some form of open thoracotomy. More recently, several minimally invasive techniques have been developed. Catheter-based device closure, in which a catheter is percutaneously guided to the defect and a patch is deployed to seal the ASD, is a technique that has been shown to successfully correct large ASDs of up to 40 mm in size.⁴ Robotic procedures have also been developed to correct ASDs through much smaller incisions.⁵ Both of these techniques require a significant rim of residual septal tissue around the defect.

Individualized approach. Since our patient had a rather large ASD that did not have sufficient residual septal rim tissue, percutaneous and robotic approaches were not feasible. Instead, he required more invasive cardiothoracic surgery. In cases such as this, the exact technique and type of incision (sternotomy vs access through the lateral chest wall) depend on age, gender, and the presence of other comorbidities.⁶

Our patient. Because there was concern that any approach other than a median one might not afford enough space to fix an ASD of such considerable size, our patient underwent a median sternotomy by a pediatric cardiothoracic surgeon who specialized in these repairs (in children as well as young adults). During the procedure, the ASD was accessed and confirmed to be as large as predicted by diagnostic imaging. A surgical patch was sutured in place to correct the defect. There were no intra-operative or postop complications.

Four weeks later, the patient had a mild pericardial effusion that was managed medically with daily furosemide and aspirin. At his 8-week postop appointment, the fluid accumulation had resolved, and he was completely asymptomatic. The patient returned to full-time active duty in the US Navy.

THE TAKEAWAY

Adults with rather large ASDs can present in a relatively asymptomatic manner and report none of the classic complaints (angina, dyspnea, fatigue). They may even engage in heavy exertional activity with no difficulty. The underlying defect may be discovered incidentally on exam by noting a split of the S2 on auscultation. If pulmonary hypertension exists, the clinician may also note a loud S2. An exam that raises suspicion for an ASD can then be followed by tests that solidify the diagnosis. Surgery is usually necessary to correct an ASD in an adult who is symptomatic or exhibits significant cardiopulmonary strain.

ILLUSTRATIVE CASE

A 24-year-old G2P1 at 24 weeks’ gestation presents to your clinic for a routine prenatal visit. Her older daughter has asthma and she is inquiring as to whether there is anything she can do to lower the risk of her second child developing asthma in the future. What do you recommend?

Asthma is the most common chronic disease in children in resource-rich countries such as the United States.² The Centers for Disease Control and Prevention (CDC) reported that 8.4% of children were diagnosed with asthma in 2015.³

Omega-3 fatty acids, found naturally in fish oil, are thought to confer anti-inflammatory properties that offer protection against asthma. Clinical trials have shown that fish oil supplementation in pregnancy results in higher levels of omega-3 fatty acids, along with anti-inflammatory changes, in offspring.⁴ Previous epidemiologic studies have also found that consumption of omega-3 fatty acids decreased the risk of atopy and asthma in offspring.^5,6

A Cochrane review published in 2015, however, concluded that omega-3 supplementation during pregnancy had no benefit on wheeze or asthma in offspring.⁷ Five RCTs were included in the analysis. The largest trial by Palmer et al, which included 706 women, showed no benefit for omega-3 supplementation.⁸ The second largest by Olsen et al, which included 533 women, did show a benefit (hazard ratio [HR]=0.37; 95% confidence interval [CI], 0.15-0.92; number needed to treat [NNT]=19.6).⁹

These results, however, were limited by heterogeneity in the amount of fish oil supplemented and duration of follow-up. For example, the children in the Palmer study were followed only until 3 years of age, which is around the time that asthma can be formally diagnosed, potentially leading to under-reporting.⁸ In addition, the diagnosis of asthma was based on parent report of 3 episodes of wheezing, use of daily asthma medication, or use of a national registry—all of which can underestimate the incidence of asthma. The reported rate of childhood asthma with IgE-sensitization (they did not report the rate without sensitization) was 1.8% in both arms, which is much lower than the CDC’s rate of 8.4%, suggesting underdiagnosis.^3,8 Due to these biases and other potential confounders, no firm conclusions can be drawn from the Cochrane review.

STUDY SUMMARY

Maternal fish oil supplementation reduces incidence of asthma in children

This single-center, double-blinded RCT of 736 pregnant women evaluated the effect of 2.4 g/d of n-3 long-chain polyunsaturated fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) or placebo (olive oil), starting at an estimated gestational age of 24 to 26 weeks, on wheeze or asthma incidence in their offspring.¹

Eligible women were between 22 and 26 weeks’ pregnant at the time of recruitment. Exclusion criteria included supplementation of 600 IU/d or more of vitamin D, or having any endocrine, cardiac, or renal disorders. The investigators randomized the women in a 1:1 ratio to either fish oil or placebo. Maternal EPA and DHA blood levels were tested at the time of randomization and one week after birth.

The primary outcome was persistent wheeze or asthma (after 3 years of age, the diagnosis of persistent wheeze was termed asthma) based on daily diary recordings of 5 episodes of troublesome lung symptoms within the last 6 months (each lasting for at least 3 consecutive days), rescue use of inhaled beta₂-agonists, and/or relapse after a 3-month course of inhaled glucocorticoids. Secondary outcomes included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.

In total, 695 offspring were included in the study with 95.5% follow-up at 3 years and 93.1% follow-up at 5 years. The children had scheduled pediatric visits at 1 week; 1, 3, 6, 12, 18, 24, 30, and 36 months; and at 4 and 5 years, and acute visits for any pulmonary, allergic, or dermatologic symptoms that arose.

Results. The investigators found that the children of the mothers who received the fish oil had a lower risk of persistent wheeze or asthma at ages 3 to 5 years compared to those who received placebo (16.9% vs 23.7%; HR=0.69; 95% CI, 0.49-0.97; P=.035; NNT=14.7). But the effect of the fish oil supplementation was significant only in the children of the mothers with baseline EPA and DHA levels in the lowest third (17.5% vs 34.1%; HR=0.46; 95% CI, 0.25-0.83; P=.011; NNT=5.6). Similarly, in mothers who consumed the least EPA and DHA before the start of the study, fish oil supplementation had a greater benefit in terms of decreased wheeze and asthma (18.5% vs 32.4%; HR=0.55; 95% CI, 0.30-0.98; P=.043; NNT=7.2).

As for the secondary outcomes, only a reduction in lower respiratory tract infections was associated with the fish oil supplementation vs the control (38.8% vs 45.5%; HR=0.77; 95% CI, 0.61-0.99; P=.041; NNT=14.9). There was no reduction in asthma exacerbations, eczema, or risk of sensitization in the fish oil group.

WHAT'S NEW?

Study adds fuel to the fire

This study strengthens the case for fish oil supplementation during pregnancy to reduce the risk of asthma in offspring, despite the recent Cochrane review that showed no benefit.^1,7 The Palmer study used a much lower amount of omega-3s (900 mg/d fish oil vs 2400 mg/d in the current trial).^1,8 Olsen et al supplemented with a greater amount of omega-3s (2700 mg/d) and did find a benefit.⁹ The NNT from the Olsen study (19.6) is consistent with that of the current investigation, suggesting that a higher dosage may be necessary to prevent the onset of asthma.

This study strengthens the case for fish oil supplementation during pregnancy to reduce the risk of asthma in children.

Additionally, this study followed children for a longer period than did the Palmer study, which may have led to more accurate diagnoses of asthma.^1,8 Lastly, the diagnosis of asthma in the Palmer study was based on parent survey data and use of daily asthma medicine rather than on daily diary cards, which are often more accurate.

Consider fish consumption. Both this study and the Olsen trial were performed in Denmark.^1,9 While Denmark and the United States have had a relatively similar level of fish consumption since the 1990s, women in Denmark may eat a higher proportion of oily fish than women in the United States, given the more common inclusion of mackerel and herring in their diet.¹⁰ Thus, the effect of supplementation may be more pronounced in women in the United States.

CAVEATS

Questions remain: Ideal dose and which women to treat?

The US Food and Drug Administration currently recommends 8 to 12 ounces of fish per week for pregnant women, but there are no guidelines on the ideal amount of fish oil to be consumed.¹¹ The Palmer study,⁸ using 900 mg/d fish oil, did not show a benefit, whereas there did appear to be benefit in this study (2400 mg/d)¹ and the Olsen study (2700 mg/d).⁹ Further research is needed to determine the optimal dosage.

Only women whose blood levels of EPA and DHA are low to begin with will likely benefit from this intervention.

The decreased risk of persistent wheeze or asthma was seen only in the children of the women whose EPA and DHA blood levels were in the lowest third of the study population. Thus, only women whose blood levels are low to begin with will likely benefit from this intervention. Currently, EPA and DHA levels are not routinely checked, but there may be some benefit to doing so.

One proxy for blood levels is maternal intake of fish at baseline. The investigators found that there was an association between dietary intake of fish and blood levels of EPA and DHA (r=0.32; P<.001).¹ Therefore, additional screening questions to determine fish consumption would be useful for identifying women most likely to benefit from supplementation.

CHALLENGES TO IMPLEMENTATION

Multiple pills and additional cost

Since omega-3 fatty acids are relatively safe and the NNT in the general population is low, it may be worth supplementing all pregnant women, even without a commercially-available blood test for EPA or DHA. Nevertheless, some women may find it challenging to take up to an additional 4 pills/d for 13 or more weeks. Also, there is an associated cost with these supplements, although it is low.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 24-year-old G2P1 at 24 weeks’ gestation presents to your clinic for a routine prenatal visit. Her older daughter has asthma and she is inquiring as to whether there is anything she can do to lower the risk of her second child developing asthma in the future. What do you recommend?

Asthma is the most common chronic disease in children in resource-rich countries such as the United States.² The Centers for Disease Control and Prevention (CDC) reported that 8.4% of children were diagnosed with asthma in 2015.³

Omega-3 fatty acids, found naturally in fish oil, are thought to confer anti-inflammatory properties that offer protection against asthma. Clinical trials have shown that fish oil supplementation in pregnancy results in higher levels of omega-3 fatty acids, along with anti-inflammatory changes, in offspring.⁴ Previous epidemiologic studies have also found that consumption of omega-3 fatty acids decreased the risk of atopy and asthma in offspring.^5,6

A Cochrane review published in 2015, however, concluded that omega-3 supplementation during pregnancy had no benefit on wheeze or asthma in offspring.⁷ Five RCTs were included in the analysis. The largest trial by Palmer et al, which included 706 women, showed no benefit for omega-3 supplementation.⁸ The second largest by Olsen et al, which included 533 women, did show a benefit (hazard ratio [HR]=0.37; 95% confidence interval [CI], 0.15-0.92; number needed to treat [NNT]=19.6).⁹

These results, however, were limited by heterogeneity in the amount of fish oil supplemented and duration of follow-up. For example, the children in the Palmer study were followed only until 3 years of age, which is around the time that asthma can be formally diagnosed, potentially leading to under-reporting.⁸ In addition, the diagnosis of asthma was based on parent report of 3 episodes of wheezing, use of daily asthma medication, or use of a national registry—all of which can underestimate the incidence of asthma. The reported rate of childhood asthma with IgE-sensitization (they did not report the rate without sensitization) was 1.8% in both arms, which is much lower than the CDC’s rate of 8.4%, suggesting underdiagnosis.^3,8 Due to these biases and other potential confounders, no firm conclusions can be drawn from the Cochrane review.

STUDY SUMMARY

Maternal fish oil supplementation reduces incidence of asthma in children

This single-center, double-blinded RCT of 736 pregnant women evaluated the effect of 2.4 g/d of n-3 long-chain polyunsaturated fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) or placebo (olive oil), starting at an estimated gestational age of 24 to 26 weeks, on wheeze or asthma incidence in their offspring.¹

Eligible women were between 22 and 26 weeks’ pregnant at the time of recruitment. Exclusion criteria included supplementation of 600 IU/d or more of vitamin D, or having any endocrine, cardiac, or renal disorders. The investigators randomized the women in a 1:1 ratio to either fish oil or placebo. Maternal EPA and DHA blood levels were tested at the time of randomization and one week after birth.

The primary outcome was persistent wheeze or asthma (after 3 years of age, the diagnosis of persistent wheeze was termed asthma) based on daily diary recordings of 5 episodes of troublesome lung symptoms within the last 6 months (each lasting for at least 3 consecutive days), rescue use of inhaled beta₂-agonists, and/or relapse after a 3-month course of inhaled glucocorticoids. Secondary outcomes included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.

In total, 695 offspring were included in the study with 95.5% follow-up at 3 years and 93.1% follow-up at 5 years. The children had scheduled pediatric visits at 1 week; 1, 3, 6, 12, 18, 24, 30, and 36 months; and at 4 and 5 years, and acute visits for any pulmonary, allergic, or dermatologic symptoms that arose.

Results. The investigators found that the children of the mothers who received the fish oil had a lower risk of persistent wheeze or asthma at ages 3 to 5 years compared to those who received placebo (16.9% vs 23.7%; HR=0.69; 95% CI, 0.49-0.97; P=.035; NNT=14.7). But the effect of the fish oil supplementation was significant only in the children of the mothers with baseline EPA and DHA levels in the lowest third (17.5% vs 34.1%; HR=0.46; 95% CI, 0.25-0.83; P=.011; NNT=5.6). Similarly, in mothers who consumed the least EPA and DHA before the start of the study, fish oil supplementation had a greater benefit in terms of decreased wheeze and asthma (18.5% vs 32.4%; HR=0.55; 95% CI, 0.30-0.98; P=.043; NNT=7.2).

As for the secondary outcomes, only a reduction in lower respiratory tract infections was associated with the fish oil supplementation vs the control (38.8% vs 45.5%; HR=0.77; 95% CI, 0.61-0.99; P=.041; NNT=14.9). There was no reduction in asthma exacerbations, eczema, or risk of sensitization in the fish oil group.

WHAT'S NEW?

Study adds fuel to the fire

This study strengthens the case for fish oil supplementation during pregnancy to reduce the risk of asthma in offspring, despite the recent Cochrane review that showed no benefit.^1,7 The Palmer study used a much lower amount of omega-3s (900 mg/d fish oil vs 2400 mg/d in the current trial).^1,8 Olsen et al supplemented with a greater amount of omega-3s (2700 mg/d) and did find a benefit.⁹ The NNT from the Olsen study (19.6) is consistent with that of the current investigation, suggesting that a higher dosage may be necessary to prevent the onset of asthma.

This study strengthens the case for fish oil supplementation during pregnancy to reduce the risk of asthma in children.

Additionally, this study followed children for a longer period than did the Palmer study, which may have led to more accurate diagnoses of asthma.^1,8 Lastly, the diagnosis of asthma in the Palmer study was based on parent survey data and use of daily asthma medicine rather than on daily diary cards, which are often more accurate.

Consider fish consumption. Both this study and the Olsen trial were performed in Denmark.^1,9 While Denmark and the United States have had a relatively similar level of fish consumption since the 1990s, women in Denmark may eat a higher proportion of oily fish than women in the United States, given the more common inclusion of mackerel and herring in their diet.¹⁰ Thus, the effect of supplementation may be more pronounced in women in the United States.

CAVEATS

Questions remain: Ideal dose and which women to treat?

The US Food and Drug Administration currently recommends 8 to 12 ounces of fish per week for pregnant women, but there are no guidelines on the ideal amount of fish oil to be consumed.¹¹ The Palmer study,⁸ using 900 mg/d fish oil, did not show a benefit, whereas there did appear to be benefit in this study (2400 mg/d)¹ and the Olsen study (2700 mg/d).⁹ Further research is needed to determine the optimal dosage.

Only women whose blood levels of EPA and DHA are low to begin with will likely benefit from this intervention.

The decreased risk of persistent wheeze or asthma was seen only in the children of the women whose EPA and DHA blood levels were in the lowest third of the study population. Thus, only women whose blood levels are low to begin with will likely benefit from this intervention. Currently, EPA and DHA levels are not routinely checked, but there may be some benefit to doing so.

One proxy for blood levels is maternal intake of fish at baseline. The investigators found that there was an association between dietary intake of fish and blood levels of EPA and DHA (r=0.32; P<.001).¹ Therefore, additional screening questions to determine fish consumption would be useful for identifying women most likely to benefit from supplementation.

CHALLENGES TO IMPLEMENTATION

Multiple pills and additional cost

Since omega-3 fatty acids are relatively safe and the NNT in the general population is low, it may be worth supplementing all pregnant women, even without a commercially-available blood test for EPA or DHA. Nevertheless, some women may find it challenging to take up to an additional 4 pills/d for 13 or more weeks. Also, there is an associated cost with these supplements, although it is low.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 24-year-old G2P1 at 24 weeks’ gestation presents to your clinic for a routine prenatal visit. Her older daughter has asthma and she is inquiring as to whether there is anything she can do to lower the risk of her second child developing asthma in the future. What do you recommend?

Asthma is the most common chronic disease in children in resource-rich countries such as the United States.² The Centers for Disease Control and Prevention (CDC) reported that 8.4% of children were diagnosed with asthma in 2015.³

Omega-3 fatty acids, found naturally in fish oil, are thought to confer anti-inflammatory properties that offer protection against asthma. Clinical trials have shown that fish oil supplementation in pregnancy results in higher levels of omega-3 fatty acids, along with anti-inflammatory changes, in offspring.⁴ Previous epidemiologic studies have also found that consumption of omega-3 fatty acids decreased the risk of atopy and asthma in offspring.^5,6

A Cochrane review published in 2015, however, concluded that omega-3 supplementation during pregnancy had no benefit on wheeze or asthma in offspring.⁷ Five RCTs were included in the analysis. The largest trial by Palmer et al, which included 706 women, showed no benefit for omega-3 supplementation.⁸ The second largest by Olsen et al, which included 533 women, did show a benefit (hazard ratio [HR]=0.37; 95% confidence interval [CI], 0.15-0.92; number needed to treat [NNT]=19.6).⁹

These results, however, were limited by heterogeneity in the amount of fish oil supplemented and duration of follow-up. For example, the children in the Palmer study were followed only until 3 years of age, which is around the time that asthma can be formally diagnosed, potentially leading to under-reporting.⁸ In addition, the diagnosis of asthma was based on parent report of 3 episodes of wheezing, use of daily asthma medication, or use of a national registry—all of which can underestimate the incidence of asthma. The reported rate of childhood asthma with IgE-sensitization (they did not report the rate without sensitization) was 1.8% in both arms, which is much lower than the CDC’s rate of 8.4%, suggesting underdiagnosis.^3,8 Due to these biases and other potential confounders, no firm conclusions can be drawn from the Cochrane review.

STUDY SUMMARY

Maternal fish oil supplementation reduces incidence of asthma in children

This single-center, double-blinded RCT of 736 pregnant women evaluated the effect of 2.4 g/d of n-3 long-chain polyunsaturated fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) or placebo (olive oil), starting at an estimated gestational age of 24 to 26 weeks, on wheeze or asthma incidence in their offspring.¹

Eligible women were between 22 and 26 weeks’ pregnant at the time of recruitment. Exclusion criteria included supplementation of 600 IU/d or more of vitamin D, or having any endocrine, cardiac, or renal disorders. The investigators randomized the women in a 1:1 ratio to either fish oil or placebo. Maternal EPA and DHA blood levels were tested at the time of randomization and one week after birth.

The primary outcome was persistent wheeze or asthma (after 3 years of age, the diagnosis of persistent wheeze was termed asthma) based on daily diary recordings of 5 episodes of troublesome lung symptoms within the last 6 months (each lasting for at least 3 consecutive days), rescue use of inhaled beta₂-agonists, and/or relapse after a 3-month course of inhaled glucocorticoids. Secondary outcomes included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.

In total, 695 offspring were included in the study with 95.5% follow-up at 3 years and 93.1% follow-up at 5 years. The children had scheduled pediatric visits at 1 week; 1, 3, 6, 12, 18, 24, 30, and 36 months; and at 4 and 5 years, and acute visits for any pulmonary, allergic, or dermatologic symptoms that arose.

Results. The investigators found that the children of the mothers who received the fish oil had a lower risk of persistent wheeze or asthma at ages 3 to 5 years compared to those who received placebo (16.9% vs 23.7%; HR=0.69; 95% CI, 0.49-0.97; P=.035; NNT=14.7). But the effect of the fish oil supplementation was significant only in the children of the mothers with baseline EPA and DHA levels in the lowest third (17.5% vs 34.1%; HR=0.46; 95% CI, 0.25-0.83; P=.011; NNT=5.6). Similarly, in mothers who consumed the least EPA and DHA before the start of the study, fish oil supplementation had a greater benefit in terms of decreased wheeze and asthma (18.5% vs 32.4%; HR=0.55; 95% CI, 0.30-0.98; P=.043; NNT=7.2).

As for the secondary outcomes, only a reduction in lower respiratory tract infections was associated with the fish oil supplementation vs the control (38.8% vs 45.5%; HR=0.77; 95% CI, 0.61-0.99; P=.041; NNT=14.9). There was no reduction in asthma exacerbations, eczema, or risk of sensitization in the fish oil group.

WHAT'S NEW?

Study adds fuel to the fire

This study strengthens the case for fish oil supplementation during pregnancy to reduce the risk of asthma in offspring, despite the recent Cochrane review that showed no benefit.^1,7 The Palmer study used a much lower amount of omega-3s (900 mg/d fish oil vs 2400 mg/d in the current trial).^1,8 Olsen et al supplemented with a greater amount of omega-3s (2700 mg/d) and did find a benefit.⁹ The NNT from the Olsen study (19.6) is consistent with that of the current investigation, suggesting that a higher dosage may be necessary to prevent the onset of asthma.

This study strengthens the case for fish oil supplementation during pregnancy to reduce the risk of asthma in children.

Additionally, this study followed children for a longer period than did the Palmer study, which may have led to more accurate diagnoses of asthma.^1,8 Lastly, the diagnosis of asthma in the Palmer study was based on parent survey data and use of daily asthma medicine rather than on daily diary cards, which are often more accurate.

Consider fish consumption. Both this study and the Olsen trial were performed in Denmark.^1,9 While Denmark and the United States have had a relatively similar level of fish consumption since the 1990s, women in Denmark may eat a higher proportion of oily fish than women in the United States, given the more common inclusion of mackerel and herring in their diet.¹⁰ Thus, the effect of supplementation may be more pronounced in women in the United States.

CAVEATS

Questions remain: Ideal dose and which women to treat?

The US Food and Drug Administration currently recommends 8 to 12 ounces of fish per week for pregnant women, but there are no guidelines on the ideal amount of fish oil to be consumed.¹¹ The Palmer study,⁸ using 900 mg/d fish oil, did not show a benefit, whereas there did appear to be benefit in this study (2400 mg/d)¹ and the Olsen study (2700 mg/d).⁹ Further research is needed to determine the optimal dosage.

Only women whose blood levels of EPA and DHA are low to begin with will likely benefit from this intervention.

The decreased risk of persistent wheeze or asthma was seen only in the children of the women whose EPA and DHA blood levels were in the lowest third of the study population. Thus, only women whose blood levels are low to begin with will likely benefit from this intervention. Currently, EPA and DHA levels are not routinely checked, but there may be some benefit to doing so.

One proxy for blood levels is maternal intake of fish at baseline. The investigators found that there was an association between dietary intake of fish and blood levels of EPA and DHA (r=0.32; P<.001).¹ Therefore, additional screening questions to determine fish consumption would be useful for identifying women most likely to benefit from supplementation.

CHALLENGES TO IMPLEMENTATION

Multiple pills and additional cost

Since omega-3 fatty acids are relatively safe and the NNT in the general population is low, it may be worth supplementing all pregnant women, even without a commercially-available blood test for EPA or DHA. Nevertheless, some women may find it challenging to take up to an additional 4 pills/d for 13 or more weeks. Also, there is an associated cost with these supplements, although it is low.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

A single 30-minute coaching session with a physiotherapist within 6 weeks of major upper abdominal surgery significantly reduced postoperative pulmonary complications (PPC), according to the results of a prospective trial.

Ianthe Boden and her colleagues recruited 441 eligible adults scheduled for elective major upper abdominal surgery to participate in the prospective, multicenter, double-blinded, controlled superiority study to assess whether PPC outcomes were affected by preoperative physiotherapy. Consecutive participants were obtained from outpatient preadmission assessment clinics during June 2013 to August 2015; they were assigned randomly in a 1:1 ratio to the control (219) or intervention (222) groups. The median patient age was 68 years for the control and 63 for the intervention group, and each group was composed of 31% women.

monkeybusinessimages/Thinkstock

SOURCE: Boden I et al. BMJ. 2018. doi: 10.1136/bmj.j5916.

A single 30-minute coaching session with a physiotherapist within 6 weeks of major upper abdominal surgery significantly reduced postoperative pulmonary complications (PPC), according to the results of a prospective trial.

Ianthe Boden and her colleagues recruited 441 eligible adults scheduled for elective major upper abdominal surgery to participate in the prospective, multicenter, double-blinded, controlled superiority study to assess whether PPC outcomes were affected by preoperative physiotherapy. Consecutive participants were obtained from outpatient preadmission assessment clinics during June 2013 to August 2015; they were assigned randomly in a 1:1 ratio to the control (219) or intervention (222) groups. The median patient age was 68 years for the control and 63 for the intervention group, and each group was composed of 31% women.

monkeybusinessimages/Thinkstock

SOURCE: Boden I et al. BMJ. 2018. doi: 10.1136/bmj.j5916.

A single 30-minute coaching session with a physiotherapist within 6 weeks of major upper abdominal surgery significantly reduced postoperative pulmonary complications (PPC), according to the results of a prospective trial.

Ianthe Boden and her colleagues recruited 441 eligible adults scheduled for elective major upper abdominal surgery to participate in the prospective, multicenter, double-blinded, controlled superiority study to assess whether PPC outcomes were affected by preoperative physiotherapy. Consecutive participants were obtained from outpatient preadmission assessment clinics during June 2013 to August 2015; they were assigned randomly in a 1:1 ratio to the control (219) or intervention (222) groups. The median patient age was 68 years for the control and 63 for the intervention group, and each group was composed of 31% women.

monkeybusinessimages/Thinkstock

SOURCE: Boden I et al. BMJ. 2018. doi: 10.1136/bmj.j5916.

The influenza vaccine introduced in 2009 showed reduced effectiveness during the 2015-2016 influenza season, but only in adults born between 1958 and 1979, according to an analysis published online in the Journal of Infectious Diseases.

Using the Influenza Vaccine Effectiveness Network, researchers analyzed data from 2,115 patients with medically attended acute respiratory illness who tested positive for A(H1N1)pdm09 influenza virus, and 14,696 patients who tested negative for the influenza virus, from 2010-2011 to 2015-2016 (excluding the 2014-2015 influenza season).

Overall, 48% of the influenza virus–negative patients and 28% of the virus-positive patients had received at least one dose of the seasonal inactivated influenza vaccine more than 2 weeks before they fell ill.

However, the vaccine, which was based on the A/California/07/2009 strain of the A(H1N1)pdm09 virus, was only 47% effective during the 2015-2016 season, compared with 61% effectiveness during the 2010-2011 season through to the 2013-2014 season.

When researchers looked at vaccine effectiveness by birth cohort, they found that one particular cohort – individuals born between 1958 and 1979 – showed a significantly reduced vaccine effectiveness (22%) during the 2015-2016 season. By comparison, vaccine effectiveness in this cohort was 61% during the 2010-2013 seasons, and 56% during the 2013-2014 season.

When this birth cohort was excluded from analysis of the 2015-2016 season, the overall vaccine effectiveness for that season was 61%.

While the vaccine was based on an early reference strain of A(H1N1)pdm09, the virus itself later acquired mutations in the hemagglutinin gene, leading to the emergence of new genetic clades, including 6B, which dominated in the 2013-2014 influenza season, and 6B.1, which dominated in 2015-2016.

“Limited serologic data suggest that some adults born during 1958-1979 (age range in 2015-2016, 36-57 years) have decreased antibody titers against A(H1N1)pdm09 group 6B and 6B.1 viruses,” wrote Brendan Flannery, PhD, from the Centers for Disease Control and Prevention, and his coauthors.

They suggested that individuals in this cohort may have been immunologically primed with A/USSR/90/1977-like viruses, which were the first group of A(H1N1) viruses that this cohort would have been exposed to. A(H1N1) strains didn’t circulate between 1958 and 1977. Vaccination with A(H1N1)pdm09 viruses may have induced antibodies against shared antigenic components found on early versions of A(H1N1)pdm09.

If these shared antigenic epitopes were then altered in the later 6B and 6B.1 viruses, that might account for decreased antibody titers in this age group.

“Replacement of the A/California/07/2009(H1N1)pdm09 vaccine reference strain with A/Michigan/45/2015 (group 6B.1) should lead to improved [vaccine effectiveness] against circulating A(H1N1)pdm09 viruses,” the investigators noted.

The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Eight authors declared funding, grants, and consultancies with the pharmaceutical industry, with five also declaring funding from the CDC.

SOURCE: Flannery B et al. J Infect Dis. 2018 Jan 18. doi: 10.1093/infdis/jix634.

The influenza vaccine introduced in 2009 showed reduced effectiveness during the 2015-2016 influenza season, but only in adults born between 1958 and 1979, according to an analysis published online in the Journal of Infectious Diseases.

Using the Influenza Vaccine Effectiveness Network, researchers analyzed data from 2,115 patients with medically attended acute respiratory illness who tested positive for A(H1N1)pdm09 influenza virus, and 14,696 patients who tested negative for the influenza virus, from 2010-2011 to 2015-2016 (excluding the 2014-2015 influenza season).

Overall, 48% of the influenza virus–negative patients and 28% of the virus-positive patients had received at least one dose of the seasonal inactivated influenza vaccine more than 2 weeks before they fell ill.

However, the vaccine, which was based on the A/California/07/2009 strain of the A(H1N1)pdm09 virus, was only 47% effective during the 2015-2016 season, compared with 61% effectiveness during the 2010-2011 season through to the 2013-2014 season.

When researchers looked at vaccine effectiveness by birth cohort, they found that one particular cohort – individuals born between 1958 and 1979 – showed a significantly reduced vaccine effectiveness (22%) during the 2015-2016 season. By comparison, vaccine effectiveness in this cohort was 61% during the 2010-2013 seasons, and 56% during the 2013-2014 season.

When this birth cohort was excluded from analysis of the 2015-2016 season, the overall vaccine effectiveness for that season was 61%.

While the vaccine was based on an early reference strain of A(H1N1)pdm09, the virus itself later acquired mutations in the hemagglutinin gene, leading to the emergence of new genetic clades, including 6B, which dominated in the 2013-2014 influenza season, and 6B.1, which dominated in 2015-2016.

“Limited serologic data suggest that some adults born during 1958-1979 (age range in 2015-2016, 36-57 years) have decreased antibody titers against A(H1N1)pdm09 group 6B and 6B.1 viruses,” wrote Brendan Flannery, PhD, from the Centers for Disease Control and Prevention, and his coauthors.

They suggested that individuals in this cohort may have been immunologically primed with A/USSR/90/1977-like viruses, which were the first group of A(H1N1) viruses that this cohort would have been exposed to. A(H1N1) strains didn’t circulate between 1958 and 1977. Vaccination with A(H1N1)pdm09 viruses may have induced antibodies against shared antigenic components found on early versions of A(H1N1)pdm09.

If these shared antigenic epitopes were then altered in the later 6B and 6B.1 viruses, that might account for decreased antibody titers in this age group.

“Replacement of the A/California/07/2009(H1N1)pdm09 vaccine reference strain with A/Michigan/45/2015 (group 6B.1) should lead to improved [vaccine effectiveness] against circulating A(H1N1)pdm09 viruses,” the investigators noted.

The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Eight authors declared funding, grants, and consultancies with the pharmaceutical industry, with five also declaring funding from the CDC.

SOURCE: Flannery B et al. J Infect Dis. 2018 Jan 18. doi: 10.1093/infdis/jix634.

The influenza vaccine introduced in 2009 showed reduced effectiveness during the 2015-2016 influenza season, but only in adults born between 1958 and 1979, according to an analysis published online in the Journal of Infectious Diseases.

Using the Influenza Vaccine Effectiveness Network, researchers analyzed data from 2,115 patients with medically attended acute respiratory illness who tested positive for A(H1N1)pdm09 influenza virus, and 14,696 patients who tested negative for the influenza virus, from 2010-2011 to 2015-2016 (excluding the 2014-2015 influenza season).

Overall, 48% of the influenza virus–negative patients and 28% of the virus-positive patients had received at least one dose of the seasonal inactivated influenza vaccine more than 2 weeks before they fell ill.

However, the vaccine, which was based on the A/California/07/2009 strain of the A(H1N1)pdm09 virus, was only 47% effective during the 2015-2016 season, compared with 61% effectiveness during the 2010-2011 season through to the 2013-2014 season.

When researchers looked at vaccine effectiveness by birth cohort, they found that one particular cohort – individuals born between 1958 and 1979 – showed a significantly reduced vaccine effectiveness (22%) during the 2015-2016 season. By comparison, vaccine effectiveness in this cohort was 61% during the 2010-2013 seasons, and 56% during the 2013-2014 season.

When this birth cohort was excluded from analysis of the 2015-2016 season, the overall vaccine effectiveness for that season was 61%.

While the vaccine was based on an early reference strain of A(H1N1)pdm09, the virus itself later acquired mutations in the hemagglutinin gene, leading to the emergence of new genetic clades, including 6B, which dominated in the 2013-2014 influenza season, and 6B.1, which dominated in 2015-2016.

“Limited serologic data suggest that some adults born during 1958-1979 (age range in 2015-2016, 36-57 years) have decreased antibody titers against A(H1N1)pdm09 group 6B and 6B.1 viruses,” wrote Brendan Flannery, PhD, from the Centers for Disease Control and Prevention, and his coauthors.

They suggested that individuals in this cohort may have been immunologically primed with A/USSR/90/1977-like viruses, which were the first group of A(H1N1) viruses that this cohort would have been exposed to. A(H1N1) strains didn’t circulate between 1958 and 1977. Vaccination with A(H1N1)pdm09 viruses may have induced antibodies against shared antigenic components found on early versions of A(H1N1)pdm09.

If these shared antigenic epitopes were then altered in the later 6B and 6B.1 viruses, that might account for decreased antibody titers in this age group.

“Replacement of the A/California/07/2009(H1N1)pdm09 vaccine reference strain with A/Michigan/45/2015 (group 6B.1) should lead to improved [vaccine effectiveness] against circulating A(H1N1)pdm09 viruses,” the investigators noted.

The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Eight authors declared funding, grants, and consultancies with the pharmaceutical industry, with five also declaring funding from the CDC.

SOURCE: Flannery B et al. J Infect Dis. 2018 Jan 18. doi: 10.1093/infdis/jix634.

Influenza activity continued to increase in the week ending Jan. 20, and the 2017-2018 flu season continues to look a lot like the 2009-2010 pandemic, according to data from the Centers for Disease Control and Prevention.

That season was dominated by influenza A (H3N2), and the 2017-2018 season seems to be going down that same path. For the week ending Jan. 20, the proportion of outpatient visits for influenza-like illness increased to 6.6%, which is, for the second consecutive week, the highest level reported since October of – you guessed it – 2009, when it hit 7.7%, the CDC said in its weekly flu surveillance report.

The level reported last week, 6.3%, has been revised downward and now stands at an even 6%.

It turns out that 2018 is something of a milestone for the H3N2 virus. The virus first emerged in 1968, so it has reached its 50th anniversary, Dan Jernigan, MD, director of the influenza division at the CDC’s National Center for Immunization and Respiratory Diseases, Atlanta, said on Jan. 26 in a weekly briefing.

H3N2 must not be happy about hitting the big 5-0, however, because the map of influenza-like illness activity looks pretty red and angry. For the week ending Jan. 20, there were 30 states at the highest level of flu activity on the CDC’s 1-10 scale, with another nine in the “high” range at levels 8 and 9.

Dr. Jernigan did suggest that activity may have peaked in some areas of the country, with California among them.

There were seven pediatric deaths reported for the week ending Jan. 20, although six occurred in previous weeks. There have been 37 flu-related deaths among children so far during the 2017-2018 season, the CDC said.

[email protected]

Influenza activity continued to increase in the week ending Jan. 20, and the 2017-2018 flu season continues to look a lot like the 2009-2010 pandemic, according to data from the Centers for Disease Control and Prevention.

That season was dominated by influenza A (H3N2), and the 2017-2018 season seems to be going down that same path. For the week ending Jan. 20, the proportion of outpatient visits for influenza-like illness increased to 6.6%, which is, for the second consecutive week, the highest level reported since October of – you guessed it – 2009, when it hit 7.7%, the CDC said in its weekly flu surveillance report.

The level reported last week, 6.3%, has been revised downward and now stands at an even 6%.

It turns out that 2018 is something of a milestone for the H3N2 virus. The virus first emerged in 1968, so it has reached its 50th anniversary, Dan Jernigan, MD, director of the influenza division at the CDC’s National Center for Immunization and Respiratory Diseases, Atlanta, said on Jan. 26 in a weekly briefing.

H3N2 must not be happy about hitting the big 5-0, however, because the map of influenza-like illness activity looks pretty red and angry. For the week ending Jan. 20, there were 30 states at the highest level of flu activity on the CDC’s 1-10 scale, with another nine in the “high” range at levels 8 and 9.

Dr. Jernigan did suggest that activity may have peaked in some areas of the country, with California among them.

There were seven pediatric deaths reported for the week ending Jan. 20, although six occurred in previous weeks. There have been 37 flu-related deaths among children so far during the 2017-2018 season, the CDC said.

[email protected]

Influenza activity continued to increase in the week ending Jan. 20, and the 2017-2018 flu season continues to look a lot like the 2009-2010 pandemic, according to data from the Centers for Disease Control and Prevention.

That season was dominated by influenza A (H3N2), and the 2017-2018 season seems to be going down that same path. For the week ending Jan. 20, the proportion of outpatient visits for influenza-like illness increased to 6.6%, which is, for the second consecutive week, the highest level reported since October of – you guessed it – 2009, when it hit 7.7%, the CDC said in its weekly flu surveillance report.

The level reported last week, 6.3%, has been revised downward and now stands at an even 6%.

It turns out that 2018 is something of a milestone for the H3N2 virus. The virus first emerged in 1968, so it has reached its 50th anniversary, Dan Jernigan, MD, director of the influenza division at the CDC’s National Center for Immunization and Respiratory Diseases, Atlanta, said on Jan. 26 in a weekly briefing.

H3N2 must not be happy about hitting the big 5-0, however, because the map of influenza-like illness activity looks pretty red and angry. For the week ending Jan. 20, there were 30 states at the highest level of flu activity on the CDC’s 1-10 scale, with another nine in the “high” range at levels 8 and 9.

Dr. Jernigan did suggest that activity may have peaked in some areas of the country, with California among them.

There were seven pediatric deaths reported for the week ending Jan. 20, although six occurred in previous weeks. There have been 37 flu-related deaths among children so far during the 2017-2018 season, the CDC said.

[email protected]

The Food and Drug Administration has approved the use of a 250-mcg dose of roflumilast for patients with chronic obstructive pulmonary disease (COPD) for 4 weeks, followed by the use of 500-mcg therapeutic doses, according to a statement from the drug’s marketer, AstraZeneca.

The larger doses of roflumilast (Daliresp) are currently indicated for reducing the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations, according to the statement. The selective phosphodiesterase-4 inhibitor, roflumilast, was approved for this use in 500-mcg doses in 2011. The new smaller doses of the drug are being offered to help reduce the rate of treatment discontinuation with use of the higher therapeutic dosing. The 250-mcg doses of roflumilast are not to be used as treatment for COPD.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Over 12 weeks, the percentage of patients stopping treatment was significantly lower in those first given 250 mcg of roflumilast daily for 4 weeks, followed by 500 mcg once a week for 8 weeks (18.4%), compared with those given 500 mcg of roflumilast daily for 12 weeks (24.6%; odds ratio, 0.66; 95% confidence interval, 0.47-0.93; P = .017).

In eight controlled clinical trials, the most common adverse effects were diarrhea, weight loss, nausea, headache, back pain, influenza, insomnia, dizziness, and decreased appetite.

[email protected]

SOURCE: AstraZeneca press release, Jan. 24, 2018.

The Food and Drug Administration has approved the use of a 250-mcg dose of roflumilast for patients with chronic obstructive pulmonary disease (COPD) for 4 weeks, followed by the use of 500-mcg therapeutic doses, according to a statement from the drug’s marketer, AstraZeneca.

The larger doses of roflumilast (Daliresp) are currently indicated for reducing the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations, according to the statement. The selective phosphodiesterase-4 inhibitor, roflumilast, was approved for this use in 500-mcg doses in 2011. The new smaller doses of the drug are being offered to help reduce the rate of treatment discontinuation with use of the higher therapeutic dosing. The 250-mcg doses of roflumilast are not to be used as treatment for COPD.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Over 12 weeks, the percentage of patients stopping treatment was significantly lower in those first given 250 mcg of roflumilast daily for 4 weeks, followed by 500 mcg once a week for 8 weeks (18.4%), compared with those given 500 mcg of roflumilast daily for 12 weeks (24.6%; odds ratio, 0.66; 95% confidence interval, 0.47-0.93; P = .017).

In eight controlled clinical trials, the most common adverse effects were diarrhea, weight loss, nausea, headache, back pain, influenza, insomnia, dizziness, and decreased appetite.

[email protected]

SOURCE: AstraZeneca press release, Jan. 24, 2018.

The Food and Drug Administration has approved the use of a 250-mcg dose of roflumilast for patients with chronic obstructive pulmonary disease (COPD) for 4 weeks, followed by the use of 500-mcg therapeutic doses, according to a statement from the drug’s marketer, AstraZeneca.

The larger doses of roflumilast (Daliresp) are currently indicated for reducing the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations, according to the statement. The selective phosphodiesterase-4 inhibitor, roflumilast, was approved for this use in 500-mcg doses in 2011. The new smaller doses of the drug are being offered to help reduce the rate of treatment discontinuation with use of the higher therapeutic dosing. The 250-mcg doses of roflumilast are not to be used as treatment for COPD.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Over 12 weeks, the percentage of patients stopping treatment was significantly lower in those first given 250 mcg of roflumilast daily for 4 weeks, followed by 500 mcg once a week for 8 weeks (18.4%), compared with those given 500 mcg of roflumilast daily for 12 weeks (24.6%; odds ratio, 0.66; 95% confidence interval, 0.47-0.93; P = .017).

In eight controlled clinical trials, the most common adverse effects were diarrhea, weight loss, nausea, headache, back pain, influenza, insomnia, dizziness, and decreased appetite.

[email protected]

SOURCE: AstraZeneca press release, Jan. 24, 2018.

The 1-minute walk test is as effective as the 6-minute walk test at predicting transplant-free survival in patients with idiopathic pulmonary fibrosis (IPF), based on data from 179 adults. The findings were presented at the CHEST annual meeting.

The 6-minute test is often used to evaluate functional capacity in IPF patients, but is not always practical in a busy clinic setting, according to Flavia S. Nunes, MD, of Inova Fairfax Hospital in Falls Church, VA, and colleagues.

czardases/Thinkstock

The 1-minute walk test is as effective as the 6-minute walk test at predicting transplant-free survival in patients with idiopathic pulmonary fibrosis (IPF), based on data from 179 adults. The findings were presented at the CHEST annual meeting.

The 6-minute test is often used to evaluate functional capacity in IPF patients, but is not always practical in a busy clinic setting, according to Flavia S. Nunes, MD, of Inova Fairfax Hospital in Falls Church, VA, and colleagues.

czardases/Thinkstock

The 1-minute walk test is as effective as the 6-minute walk test at predicting transplant-free survival in patients with idiopathic pulmonary fibrosis (IPF), based on data from 179 adults. The findings were presented at the CHEST annual meeting.

The 6-minute test is often used to evaluate functional capacity in IPF patients, but is not always practical in a busy clinic setting, according to Flavia S. Nunes, MD, of Inova Fairfax Hospital in Falls Church, VA, and colleagues.

czardases/Thinkstock

Social media communication around lung cancer is focused primarily on cancer treatment and use of pharmaceutical and research interventions, followed closely by awareness, prevention, and risk topics, according to an analysis of Twitter conversation over a 10-day period.

Although awareness and risk prevention tweets were likely to contain cues toward action, “messages focused on treatment, end of life ... were significantly less likely to integrate cues for personal activity,” the investigators wrote. The report was published in Journal of the American College of Radiology.

©Huntstock/thinkstockphotos.com

SOURCE: Sutton J. et al., J Am Coll Radiol. 2018 Jan. doi: 10.1016/j.jacr.2017.09.043

Social media communication around lung cancer is focused primarily on cancer treatment and use of pharmaceutical and research interventions, followed closely by awareness, prevention, and risk topics, according to an analysis of Twitter conversation over a 10-day period.

Although awareness and risk prevention tweets were likely to contain cues toward action, “messages focused on treatment, end of life ... were significantly less likely to integrate cues for personal activity,” the investigators wrote. The report was published in Journal of the American College of Radiology.

©Huntstock/thinkstockphotos.com

SOURCE: Sutton J. et al., J Am Coll Radiol. 2018 Jan. doi: 10.1016/j.jacr.2017.09.043

Social media communication around lung cancer is focused primarily on cancer treatment and use of pharmaceutical and research interventions, followed closely by awareness, prevention, and risk topics, according to an analysis of Twitter conversation over a 10-day period.

Although awareness and risk prevention tweets were likely to contain cues toward action, “messages focused on treatment, end of life ... were significantly less likely to integrate cues for personal activity,” the investigators wrote. The report was published in Journal of the American College of Radiology.

©Huntstock/thinkstockphotos.com

SOURCE: Sutton J. et al., J Am Coll Radiol. 2018 Jan. doi: 10.1016/j.jacr.2017.09.043

Myocardial infarction admissions were six times more likely to occur in the week after a positive test for influenza than in the year before or the 51 weeks after the infection, according to analysis of a Canadian cohort that links laboratories with administrative databases.

The investigators used this cohort data to define definitions of “risk interval” – the first 7 days after flu detection – and a combined “control interval” – 52 weeks before the flu detection and 51 weeks after the end of the risk interval.

Among the total of 364 hospital admissions for MI in patients with confirmed influenza, 20 occurred during the defined 1-week risk interval (20 admissions/week) and 344 occurred during the control interval (3.3 admissions/week), giving an incidence ratio (IR) of 6.05, Jeffrey C. Kwong, MD, of the University of Toronto and his associates reported in the New England Journal of Medicine.

There was little difference between days 1 and 3 after flu confirmation (IR, 6.3) and days 4-7 (IR, 5.8), but risk dropped off quickly after that, with IRs of 0.6 at days 8-14 and 0.75 at days 15-28. Risk was increased for older adults, those with influenza B infection, and those who had their first MI, the investigators said.

MI incidence also was elevated after infection with noninfluenza respiratory viruses, although to a lesser extent than with influenza, which suggests that “influenza is illustrative of the role that acute respiratory infections have in precipitating acute myocardial infarction,” Dr. Kwong and his associates wrote.

The study was supported by the Canadian Institutes of Health Research, by Public Health Ontario, and by the Institute for Clinical Evaluative Sciences. Dr. Kwong reported grants from Canadian Institutes of Health Research during the conduct of the study, as well as grants from Canadian Institutes of Health Research and University of Toronto.

[email protected]

SOURCE: Kwong JC et al. N Engl J Med. 2018. 378(4):345-53. doi: 10.1056/NEJMoa1702090.

Myocardial infarction admissions were six times more likely to occur in the week after a positive test for influenza than in the year before or the 51 weeks after the infection, according to analysis of a Canadian cohort that links laboratories with administrative databases.

The investigators used this cohort data to define definitions of “risk interval” – the first 7 days after flu detection – and a combined “control interval” – 52 weeks before the flu detection and 51 weeks after the end of the risk interval.

Among the total of 364 hospital admissions for MI in patients with confirmed influenza, 20 occurred during the defined 1-week risk interval (20 admissions/week) and 344 occurred during the control interval (3.3 admissions/week), giving an incidence ratio (IR) of 6.05, Jeffrey C. Kwong, MD, of the University of Toronto and his associates reported in the New England Journal of Medicine.

There was little difference between days 1 and 3 after flu confirmation (IR, 6.3) and days 4-7 (IR, 5.8), but risk dropped off quickly after that, with IRs of 0.6 at days 8-14 and 0.75 at days 15-28. Risk was increased for older adults, those with influenza B infection, and those who had their first MI, the investigators said.

MI incidence also was elevated after infection with noninfluenza respiratory viruses, although to a lesser extent than with influenza, which suggests that “influenza is illustrative of the role that acute respiratory infections have in precipitating acute myocardial infarction,” Dr. Kwong and his associates wrote.

The study was supported by the Canadian Institutes of Health Research, by Public Health Ontario, and by the Institute for Clinical Evaluative Sciences. Dr. Kwong reported grants from Canadian Institutes of Health Research during the conduct of the study, as well as grants from Canadian Institutes of Health Research and University of Toronto.

[email protected]

SOURCE: Kwong JC et al. N Engl J Med. 2018. 378(4):345-53. doi: 10.1056/NEJMoa1702090.

Myocardial infarction admissions were six times more likely to occur in the week after a positive test for influenza than in the year before or the 51 weeks after the infection, according to analysis of a Canadian cohort that links laboratories with administrative databases.

The investigators used this cohort data to define definitions of “risk interval” – the first 7 days after flu detection – and a combined “control interval” – 52 weeks before the flu detection and 51 weeks after the end of the risk interval.

Among the total of 364 hospital admissions for MI in patients with confirmed influenza, 20 occurred during the defined 1-week risk interval (20 admissions/week) and 344 occurred during the control interval (3.3 admissions/week), giving an incidence ratio (IR) of 6.05, Jeffrey C. Kwong, MD, of the University of Toronto and his associates reported in the New England Journal of Medicine.

There was little difference between days 1 and 3 after flu confirmation (IR, 6.3) and days 4-7 (IR, 5.8), but risk dropped off quickly after that, with IRs of 0.6 at days 8-14 and 0.75 at days 15-28. Risk was increased for older adults, those with influenza B infection, and those who had their first MI, the investigators said.

MI incidence also was elevated after infection with noninfluenza respiratory viruses, although to a lesser extent than with influenza, which suggests that “influenza is illustrative of the role that acute respiratory infections have in precipitating acute myocardial infarction,” Dr. Kwong and his associates wrote.

The study was supported by the Canadian Institutes of Health Research, by Public Health Ontario, and by the Institute for Clinical Evaluative Sciences. Dr. Kwong reported grants from Canadian Institutes of Health Research during the conduct of the study, as well as grants from Canadian Institutes of Health Research and University of Toronto.

[email protected]

SOURCE: Kwong JC et al. N Engl J Med. 2018. 378(4):345-53. doi: 10.1056/NEJMoa1702090.

A 70-year-old man with chronic obstructive pulmonary disease (COPD) is admitted with increased shortness of breath. His O₂ saturation levels are usually 90%, but they’re now running 84%-88%. He has had increasing symptoms for the past 3 days.

copyright designer491/Thinkstock

What would be your next step?

A) Begin a 5-day course of corticosteroids.

B) Begin a 14-day course of corticosteroids.

C) Begin azithromycin.

D) Start BiPAP.

E) Obtain D-dimer.

This is a situation we face frequently. COPD exacerbations are a clinical diagnosis that is often jumped to as the diagnosis in patients with COPD who have increasing dyspnea. This diagnosis is frequently correct – but not always.

Patients with COPD also may be at risk for or have heart failure, which can present with identical symptoms, including widespread wheezing. We are currently in a severe influenza epidemic, and influenza can mimic a COPD exacerbation or be the trigger.

About 20 years ago, I was out of the country when one of my patients with COPD was admitted to the hospital with a COPD exacerbation. I saw him in follow-up a week after his hospitalization. He was very dyspneic and had a room air oxygen saturation of 75%. He told me his dyspnea started a few days after he had injured his leg on a wood pile in his yard.

On exam, his right leg had 3+ edema; left leg, no edema. He reported to me that he was treated for 5 days with steroids and nebulizers, with minimal change in his dyspnea. I reviewed the chart, and five physicians had seen him while he was in the hospital. Starting with the emergency department, the diagnosis was COPD exacerbation, with no differential diagnosis in any note.

The patient had multiple pulmonary emboli, and he eventually improved with anticoagulation.

In 2009, Jacques Rizkallah, MD, and his colleagues published a systematic review and meta-analysis of articles looking at the prevalence of pulmonary emboli (PE) in patients diagnosed/treated for a COPD exacerbation.¹ They found five articles comprising a total of 550 patients who met inclusion criteria. The prevalence was 19.9% (P = .014). The prevalence was much higher (24.7%) for hospitalized patients than it was for outpatients (3.3%). A very important finding in this study: There was no difference in symptoms between patients who did and did not have a pulmonary embolus.

Evrim Eylem Akpinar, MD, and colleagues studied all admissions for acute exacerbations of COPD at one hospital in Turkey over a 2-year period.² A total of 172 patients admitted for COPD exacerbations were studied. The prevalence of pulmonary embolus was 29%.

In this study, patients who were obese or immobile were more likely to have pulmonary emboli. Pleuritic chest pain and lower-limb asymmetry were signs and symptoms more commonly found in patients who had PE. Obesity was the highest independent predictor (odds ratio, 4.97) for pulmonary embolus.

Floor Aleva, MD, and colleagues recently completed a systematic review and meta-analysis on prevalence and localization of pulmonary embolus in patients with acute exacerbations of COPD.³ They found similar numbers to the previous meta-analysis (16.1%) in a total of 880 patients. They also looked at location in the lungs of the emboli and found that two-thirds of the patients had pulmonary emboli in locations that had clear indication for anticoagulation treatment.

This is important, because criticisms of earlier studies were that clinically insignificant pulmonary emboli might be being found in the studies and that they had little to do with the patients’ symptoms.

In the case presented, I think that getting a D-dimer test would be the next best step. Acute exacerbation of COPD still is the most likely diagnosis, but PE is a plausible diagnosis that should be evaluated. If the D-dimer is normal, workup for PE would be complete. If elevated, then given the 20% prevalence of PE, a CT angiography would be warranted.

Key pearl: Among patients hospitalized for COPD exacerbations, 16%-24% have pulmonary embolism.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Chest. 2009 Mar;135(3):786-93.

2. J Bras Pneumol. 2014 Jan-Feb;40(1):38-45.

3. Chest. 2017 Mar;151(3):544-54.


 

A 70-year-old man with chronic obstructive pulmonary disease (COPD) is admitted with increased shortness of breath. His O₂ saturation levels are usually 90%, but they’re now running 84%-88%. He has had increasing symptoms for the past 3 days.

copyright designer491/Thinkstock

What would be your next step?

A) Begin a 5-day course of corticosteroids.

B) Begin a 14-day course of corticosteroids.

C) Begin azithromycin.

D) Start BiPAP.

E) Obtain D-dimer.

This is a situation we face frequently. COPD exacerbations are a clinical diagnosis that is often jumped to as the diagnosis in patients with COPD who have increasing dyspnea. This diagnosis is frequently correct – but not always.

Patients with COPD also may be at risk for or have heart failure, which can present with identical symptoms, including widespread wheezing. We are currently in a severe influenza epidemic, and influenza can mimic a COPD exacerbation or be the trigger.

About 20 years ago, I was out of the country when one of my patients with COPD was admitted to the hospital with a COPD exacerbation. I saw him in follow-up a week after his hospitalization. He was very dyspneic and had a room air oxygen saturation of 75%. He told me his dyspnea started a few days after he had injured his leg on a wood pile in his yard.

On exam, his right leg had 3+ edema; left leg, no edema. He reported to me that he was treated for 5 days with steroids and nebulizers, with minimal change in his dyspnea. I reviewed the chart, and five physicians had seen him while he was in the hospital. Starting with the emergency department, the diagnosis was COPD exacerbation, with no differential diagnosis in any note.

The patient had multiple pulmonary emboli, and he eventually improved with anticoagulation.

In 2009, Jacques Rizkallah, MD, and his colleagues published a systematic review and meta-analysis of articles looking at the prevalence of pulmonary emboli (PE) in patients diagnosed/treated for a COPD exacerbation.¹ They found five articles comprising a total of 550 patients who met inclusion criteria. The prevalence was 19.9% (P = .014). The prevalence was much higher (24.7%) for hospitalized patients than it was for outpatients (3.3%). A very important finding in this study: There was no difference in symptoms between patients who did and did not have a pulmonary embolus.

Evrim Eylem Akpinar, MD, and colleagues studied all admissions for acute exacerbations of COPD at one hospital in Turkey over a 2-year period.² A total of 172 patients admitted for COPD exacerbations were studied. The prevalence of pulmonary embolus was 29%.

In this study, patients who were obese or immobile were more likely to have pulmonary emboli. Pleuritic chest pain and lower-limb asymmetry were signs and symptoms more commonly found in patients who had PE. Obesity was the highest independent predictor (odds ratio, 4.97) for pulmonary embolus.

Floor Aleva, MD, and colleagues recently completed a systematic review and meta-analysis on prevalence and localization of pulmonary embolus in patients with acute exacerbations of COPD.³ They found similar numbers to the previous meta-analysis (16.1%) in a total of 880 patients. They also looked at location in the lungs of the emboli and found that two-thirds of the patients had pulmonary emboli in locations that had clear indication for anticoagulation treatment.

This is important, because criticisms of earlier studies were that clinically insignificant pulmonary emboli might be being found in the studies and that they had little to do with the patients’ symptoms.

In the case presented, I think that getting a D-dimer test would be the next best step. Acute exacerbation of COPD still is the most likely diagnosis, but PE is a plausible diagnosis that should be evaluated. If the D-dimer is normal, workup for PE would be complete. If elevated, then given the 20% prevalence of PE, a CT angiography would be warranted.

Key pearl: Among patients hospitalized for COPD exacerbations, 16%-24% have pulmonary embolism.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Chest. 2009 Mar;135(3):786-93.

2. J Bras Pneumol. 2014 Jan-Feb;40(1):38-45.

3. Chest. 2017 Mar;151(3):544-54.


 

A 70-year-old man with chronic obstructive pulmonary disease (COPD) is admitted with increased shortness of breath. His O₂ saturation levels are usually 90%, but they’re now running 84%-88%. He has had increasing symptoms for the past 3 days.

copyright designer491/Thinkstock

What would be your next step?

A) Begin a 5-day course of corticosteroids.

B) Begin a 14-day course of corticosteroids.

C) Begin azithromycin.

D) Start BiPAP.

E) Obtain D-dimer.

This is a situation we face frequently. COPD exacerbations are a clinical diagnosis that is often jumped to as the diagnosis in patients with COPD who have increasing dyspnea. This diagnosis is frequently correct – but not always.

Patients with COPD also may be at risk for or have heart failure, which can present with identical symptoms, including widespread wheezing. We are currently in a severe influenza epidemic, and influenza can mimic a COPD exacerbation or be the trigger.

About 20 years ago, I was out of the country when one of my patients with COPD was admitted to the hospital with a COPD exacerbation. I saw him in follow-up a week after his hospitalization. He was very dyspneic and had a room air oxygen saturation of 75%. He told me his dyspnea started a few days after he had injured his leg on a wood pile in his yard.

On exam, his right leg had 3+ edema; left leg, no edema. He reported to me that he was treated for 5 days with steroids and nebulizers, with minimal change in his dyspnea. I reviewed the chart, and five physicians had seen him while he was in the hospital. Starting with the emergency department, the diagnosis was COPD exacerbation, with no differential diagnosis in any note.

The patient had multiple pulmonary emboli, and he eventually improved with anticoagulation.

In 2009, Jacques Rizkallah, MD, and his colleagues published a systematic review and meta-analysis of articles looking at the prevalence of pulmonary emboli (PE) in patients diagnosed/treated for a COPD exacerbation.¹ They found five articles comprising a total of 550 patients who met inclusion criteria. The prevalence was 19.9% (P = .014). The prevalence was much higher (24.7%) for hospitalized patients than it was for outpatients (3.3%). A very important finding in this study: There was no difference in symptoms between patients who did and did not have a pulmonary embolus.

Evrim Eylem Akpinar, MD, and colleagues studied all admissions for acute exacerbations of COPD at one hospital in Turkey over a 2-year period.² A total of 172 patients admitted for COPD exacerbations were studied. The prevalence of pulmonary embolus was 29%.

In this study, patients who were obese or immobile were more likely to have pulmonary emboli. Pleuritic chest pain and lower-limb asymmetry were signs and symptoms more commonly found in patients who had PE. Obesity was the highest independent predictor (odds ratio, 4.97) for pulmonary embolus.

Floor Aleva, MD, and colleagues recently completed a systematic review and meta-analysis on prevalence and localization of pulmonary embolus in patients with acute exacerbations of COPD.³ They found similar numbers to the previous meta-analysis (16.1%) in a total of 880 patients. They also looked at location in the lungs of the emboli and found that two-thirds of the patients had pulmonary emboli in locations that had clear indication for anticoagulation treatment.

This is important, because criticisms of earlier studies were that clinically insignificant pulmonary emboli might be being found in the studies and that they had little to do with the patients’ symptoms.

In the case presented, I think that getting a D-dimer test would be the next best step. Acute exacerbation of COPD still is the most likely diagnosis, but PE is a plausible diagnosis that should be evaluated. If the D-dimer is normal, workup for PE would be complete. If elevated, then given the 20% prevalence of PE, a CT angiography would be warranted.

Key pearl: Among patients hospitalized for COPD exacerbations, 16%-24% have pulmonary embolism.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Chest. 2009 Mar;135(3):786-93.

2. J Bras Pneumol. 2014 Jan-Feb;40(1):38-45.

3. Chest. 2017 Mar;151(3):544-54.