Pulmonary Health Hub

In patients with new-onset hypertension and obstructive sleep apnea, continuous positive airway pressure (CPAP) therapy plus antihypertensive treatment with losartan led to reductions in systolic blood pressure beyond those achieved with losartan alone, a two-phase study found.

“Adding CPAP treatment to losartan may reduce blood pressure in a clinically relevant way if the patients are compliant with the device,” said Dr. Erik Thunström of the Sahlgrenska Academy at the University of Gothenburg, Sweden, and his associates.

©viola83181/iStockphoto.com

In their open-label study, 89 men and women with new-onset untreated hypertension – 54 of whom were found to have obstructive sleep apnea (OSA) through a home sleep study and 35 of whom were determined to not have OSA – were treated for 6 weeks with losartan, 50 mg daily. Ambulatory 24-hour blood pressure monitoring was performed before and after treatment.

The patients with OSA were then randomized to receive 6 weeks of nightly add-on CPAP therapy or to continue losartan alone. Ambulatory 24-hour blood pressure monitoring was performed again.

Losartan alone reduced blood pressure in patients with hypertension and concomitant OSA, but the effect was smaller than that seen in patients without OSA. Statistically significant differences were seen in the mean net reduction in morning systolic blood pressure and morning mean arterial pressure. Overall, losartan appeared to be less effective at night and during the early morning hours in patients with OSA, the researchers reported.

After 6 weeks of losartan alone, a blood pressure less than 130/80 mm Hg was achieved by 12.5% of the patients with OSA and by 29% of the patients without OSA.

After 6 weeks of add-on CPAP therapy, 25% of patients with OSA achieved blood pressures less than 130/80 mm Hg. The differences in blood pressures for the OSA patients receiving CPAP plus losartan and those receiving losartan alone were 4.4 mm Hg for 24-hour systolic blood pressure, 1.9 mm Hg for diastolic, and 2.5 mm Hg for mean arterial pressure.

The most “robust” blood pressure changes were seen in the patients who used CPAP therapy for more than 4 hours every night, reducing the mean 24-hour systolic blood pressure by 6.5 mm Hg, the diastolic pressure by 3.8 mm Hg, and the mean arterial blood pressure by 4.6 mm Hg, the researchers reported (Am J Respir Crit Care Med. 2016 Feb.;193:310-20). “Adding CPAP to treatment with losartan reduced the mean 24-hour systolic blood pressure by 6.5 mm Hg in the subgroup of patients with OSA who were adherent with CPAP,” they wrote.

Patients included in the study all had a body mass index of 35 kg/m²; those with OSA had slightly higher BMIs that did not differ significantly from those without OSA.

That CPAP seems to have additive blood pressure–lowering effect when used concomitantly with losartan “favors the idea that it contributes to a further down-regulation of RAAS [renin-angiotensin-aldosterone system] activity in new-onset hypertension and OSA,” the authors wrote.

RAAS activity is often changed in hypertension, and in animal studies it has been shown to be up-regulated by intermittent hypoxia. Angiotensin II receptor antagonists are thus viewed as a good choice in the treatment of patients with OSA and new-onset hypertension, they wrote.

In patients with new-onset hypertension and obstructive sleep apnea, continuous positive airway pressure (CPAP) therapy plus antihypertensive treatment with losartan led to reductions in systolic blood pressure beyond those achieved with losartan alone, a two-phase study found.

“Adding CPAP treatment to losartan may reduce blood pressure in a clinically relevant way if the patients are compliant with the device,” said Dr. Erik Thunström of the Sahlgrenska Academy at the University of Gothenburg, Sweden, and his associates.

©viola83181/iStockphoto.com

In their open-label study, 89 men and women with new-onset untreated hypertension – 54 of whom were found to have obstructive sleep apnea (OSA) through a home sleep study and 35 of whom were determined to not have OSA – were treated for 6 weeks with losartan, 50 mg daily. Ambulatory 24-hour blood pressure monitoring was performed before and after treatment.

The patients with OSA were then randomized to receive 6 weeks of nightly add-on CPAP therapy or to continue losartan alone. Ambulatory 24-hour blood pressure monitoring was performed again.

Losartan alone reduced blood pressure in patients with hypertension and concomitant OSA, but the effect was smaller than that seen in patients without OSA. Statistically significant differences were seen in the mean net reduction in morning systolic blood pressure and morning mean arterial pressure. Overall, losartan appeared to be less effective at night and during the early morning hours in patients with OSA, the researchers reported.

After 6 weeks of losartan alone, a blood pressure less than 130/80 mm Hg was achieved by 12.5% of the patients with OSA and by 29% of the patients without OSA.

After 6 weeks of add-on CPAP therapy, 25% of patients with OSA achieved blood pressures less than 130/80 mm Hg. The differences in blood pressures for the OSA patients receiving CPAP plus losartan and those receiving losartan alone were 4.4 mm Hg for 24-hour systolic blood pressure, 1.9 mm Hg for diastolic, and 2.5 mm Hg for mean arterial pressure.

The most “robust” blood pressure changes were seen in the patients who used CPAP therapy for more than 4 hours every night, reducing the mean 24-hour systolic blood pressure by 6.5 mm Hg, the diastolic pressure by 3.8 mm Hg, and the mean arterial blood pressure by 4.6 mm Hg, the researchers reported (Am J Respir Crit Care Med. 2016 Feb.;193:310-20). “Adding CPAP to treatment with losartan reduced the mean 24-hour systolic blood pressure by 6.5 mm Hg in the subgroup of patients with OSA who were adherent with CPAP,” they wrote.

Patients included in the study all had a body mass index of 35 kg/m²; those with OSA had slightly higher BMIs that did not differ significantly from those without OSA.

That CPAP seems to have additive blood pressure–lowering effect when used concomitantly with losartan “favors the idea that it contributes to a further down-regulation of RAAS [renin-angiotensin-aldosterone system] activity in new-onset hypertension and OSA,” the authors wrote.

RAAS activity is often changed in hypertension, and in animal studies it has been shown to be up-regulated by intermittent hypoxia. Angiotensin II receptor antagonists are thus viewed as a good choice in the treatment of patients with OSA and new-onset hypertension, they wrote.

In patients with new-onset hypertension and obstructive sleep apnea, continuous positive airway pressure (CPAP) therapy plus antihypertensive treatment with losartan led to reductions in systolic blood pressure beyond those achieved with losartan alone, a two-phase study found.

“Adding CPAP treatment to losartan may reduce blood pressure in a clinically relevant way if the patients are compliant with the device,” said Dr. Erik Thunström of the Sahlgrenska Academy at the University of Gothenburg, Sweden, and his associates.

©viola83181/iStockphoto.com

In their open-label study, 89 men and women with new-onset untreated hypertension – 54 of whom were found to have obstructive sleep apnea (OSA) through a home sleep study and 35 of whom were determined to not have OSA – were treated for 6 weeks with losartan, 50 mg daily. Ambulatory 24-hour blood pressure monitoring was performed before and after treatment.

The patients with OSA were then randomized to receive 6 weeks of nightly add-on CPAP therapy or to continue losartan alone. Ambulatory 24-hour blood pressure monitoring was performed again.

Losartan alone reduced blood pressure in patients with hypertension and concomitant OSA, but the effect was smaller than that seen in patients without OSA. Statistically significant differences were seen in the mean net reduction in morning systolic blood pressure and morning mean arterial pressure. Overall, losartan appeared to be less effective at night and during the early morning hours in patients with OSA, the researchers reported.

After 6 weeks of losartan alone, a blood pressure less than 130/80 mm Hg was achieved by 12.5% of the patients with OSA and by 29% of the patients without OSA.

After 6 weeks of add-on CPAP therapy, 25% of patients with OSA achieved blood pressures less than 130/80 mm Hg. The differences in blood pressures for the OSA patients receiving CPAP plus losartan and those receiving losartan alone were 4.4 mm Hg for 24-hour systolic blood pressure, 1.9 mm Hg for diastolic, and 2.5 mm Hg for mean arterial pressure.

The most “robust” blood pressure changes were seen in the patients who used CPAP therapy for more than 4 hours every night, reducing the mean 24-hour systolic blood pressure by 6.5 mm Hg, the diastolic pressure by 3.8 mm Hg, and the mean arterial blood pressure by 4.6 mm Hg, the researchers reported (Am J Respir Crit Care Med. 2016 Feb.;193:310-20). “Adding CPAP to treatment with losartan reduced the mean 24-hour systolic blood pressure by 6.5 mm Hg in the subgroup of patients with OSA who were adherent with CPAP,” they wrote.

Patients included in the study all had a body mass index of 35 kg/m²; those with OSA had slightly higher BMIs that did not differ significantly from those without OSA.

That CPAP seems to have additive blood pressure–lowering effect when used concomitantly with losartan “favors the idea that it contributes to a further down-regulation of RAAS [renin-angiotensin-aldosterone system] activity in new-onset hypertension and OSA,” the authors wrote.

RAAS activity is often changed in hypertension, and in animal studies it has been shown to be up-regulated by intermittent hypoxia. Angiotensin II receptor antagonists are thus viewed as a good choice in the treatment of patients with OSA and new-onset hypertension, they wrote.

Obstructive sleep apnea syndrome (OSAS) was diagnosed in more than half of 200 active duty service members with combat-related post-traumatic stress disorder (PTSD) who were studied at Walter Reed Army Medical Center in Washington.

Compared with age-matched peers with just one of these disorders, the service members with PTSD and OSAS had poorer somnolence and sleep-related quality of life and were less adherent and responsive to positive airway pressure therapy.

©KatarzynaBialasiewicz/ Thinkstock

The findings “highlight the need for a high index of suspicion and a comprehensive approach to identifying and treating sleep-disordered breathing in these patients,” Dr. Christopher J. Lettieri of the Uniformed Services University in Bethesda, Md., and his associates wrote (Chest. 2016 Feb;149[2]:483-90). “Given the prevalence of OSAS in patients with PTSD and its adverse impact on symptoms and adherence, early identification may improve outcomes.”

In the observational cohort study, 200 consecutive active duty service members who were diagnosed with PTSD as part of post-deployment screening underwent sleep evaluations regardless of whether there was clinical suspicion of sleep-disordered breathing. More than half – about 57% – were diagnosed with OSAS. Almost 60% of the study group had mild traumatic brain injury, which has been connected in prior research to obstructive sleep apnea, and many had comorbid insomnia. Those who were diagnosed with OSAS were older and had higher BMIs than those not found to have OSAS.

All 200 patients were compared with 50 consecutive age-matched control patients who had OSAS but had not been deployed and did not have PTSD, as well as with 50 age-matched service members without prior deployment or either of the two disorders. All of the patients diagnosed with OSAS were prescribed positive airway pressure (PAP) therapy and evaluated after a month.

Sleep quality was poor in the majority of patients with PTSD, and OSAS and PTSD were both independently associated with increased daytime sleepiness and lower quality-of-life index scores. However, patients with both conditions fared significantly worse, particularly with respect to quality of life as measured by the Functional Outcomes of Sleep Questionnaire (FOSQ).

FOSQ scores were abnormal at baseline in 60% of those with PTSD and OSAS, 43% with PTSD alone, 24% with OSAS alone, and 7% of those with neither condition.

Service members with both conditions also were less likely to adhere to therapy; 30% regularly used continuous PAP therapy, compared with 55% of those who had OSAS alone.

And while continuous PAP therapy improved daytime sleepiness and quality of life in patients with both PTSD and OSAS, the degree of improvement was less than that experienced by those with OSAS alone. PTSD “represents an independent barrier to the effective treatment of OSAS and should prompt multipronged and individualized care,” they wrote.

The researchers reported having no financial disclosures.

Obstructive sleep apnea syndrome (OSAS) was diagnosed in more than half of 200 active duty service members with combat-related post-traumatic stress disorder (PTSD) who were studied at Walter Reed Army Medical Center in Washington.

Compared with age-matched peers with just one of these disorders, the service members with PTSD and OSAS had poorer somnolence and sleep-related quality of life and were less adherent and responsive to positive airway pressure therapy.

©KatarzynaBialasiewicz/ Thinkstock

The findings “highlight the need for a high index of suspicion and a comprehensive approach to identifying and treating sleep-disordered breathing in these patients,” Dr. Christopher J. Lettieri of the Uniformed Services University in Bethesda, Md., and his associates wrote (Chest. 2016 Feb;149[2]:483-90). “Given the prevalence of OSAS in patients with PTSD and its adverse impact on symptoms and adherence, early identification may improve outcomes.”

In the observational cohort study, 200 consecutive active duty service members who were diagnosed with PTSD as part of post-deployment screening underwent sleep evaluations regardless of whether there was clinical suspicion of sleep-disordered breathing. More than half – about 57% – were diagnosed with OSAS. Almost 60% of the study group had mild traumatic brain injury, which has been connected in prior research to obstructive sleep apnea, and many had comorbid insomnia. Those who were diagnosed with OSAS were older and had higher BMIs than those not found to have OSAS.

All 200 patients were compared with 50 consecutive age-matched control patients who had OSAS but had not been deployed and did not have PTSD, as well as with 50 age-matched service members without prior deployment or either of the two disorders. All of the patients diagnosed with OSAS were prescribed positive airway pressure (PAP) therapy and evaluated after a month.

Sleep quality was poor in the majority of patients with PTSD, and OSAS and PTSD were both independently associated with increased daytime sleepiness and lower quality-of-life index scores. However, patients with both conditions fared significantly worse, particularly with respect to quality of life as measured by the Functional Outcomes of Sleep Questionnaire (FOSQ).

FOSQ scores were abnormal at baseline in 60% of those with PTSD and OSAS, 43% with PTSD alone, 24% with OSAS alone, and 7% of those with neither condition.

Service members with both conditions also were less likely to adhere to therapy; 30% regularly used continuous PAP therapy, compared with 55% of those who had OSAS alone.

And while continuous PAP therapy improved daytime sleepiness and quality of life in patients with both PTSD and OSAS, the degree of improvement was less than that experienced by those with OSAS alone. PTSD “represents an independent barrier to the effective treatment of OSAS and should prompt multipronged and individualized care,” they wrote.

The researchers reported having no financial disclosures.

Obstructive sleep apnea syndrome (OSAS) was diagnosed in more than half of 200 active duty service members with combat-related post-traumatic stress disorder (PTSD) who were studied at Walter Reed Army Medical Center in Washington.

Compared with age-matched peers with just one of these disorders, the service members with PTSD and OSAS had poorer somnolence and sleep-related quality of life and were less adherent and responsive to positive airway pressure therapy.

©KatarzynaBialasiewicz/ Thinkstock

The findings “highlight the need for a high index of suspicion and a comprehensive approach to identifying and treating sleep-disordered breathing in these patients,” Dr. Christopher J. Lettieri of the Uniformed Services University in Bethesda, Md., and his associates wrote (Chest. 2016 Feb;149[2]:483-90). “Given the prevalence of OSAS in patients with PTSD and its adverse impact on symptoms and adherence, early identification may improve outcomes.”

In the observational cohort study, 200 consecutive active duty service members who were diagnosed with PTSD as part of post-deployment screening underwent sleep evaluations regardless of whether there was clinical suspicion of sleep-disordered breathing. More than half – about 57% – were diagnosed with OSAS. Almost 60% of the study group had mild traumatic brain injury, which has been connected in prior research to obstructive sleep apnea, and many had comorbid insomnia. Those who were diagnosed with OSAS were older and had higher BMIs than those not found to have OSAS.

All 200 patients were compared with 50 consecutive age-matched control patients who had OSAS but had not been deployed and did not have PTSD, as well as with 50 age-matched service members without prior deployment or either of the two disorders. All of the patients diagnosed with OSAS were prescribed positive airway pressure (PAP) therapy and evaluated after a month.

Sleep quality was poor in the majority of patients with PTSD, and OSAS and PTSD were both independently associated with increased daytime sleepiness and lower quality-of-life index scores. However, patients with both conditions fared significantly worse, particularly with respect to quality of life as measured by the Functional Outcomes of Sleep Questionnaire (FOSQ).

FOSQ scores were abnormal at baseline in 60% of those with PTSD and OSAS, 43% with PTSD alone, 24% with OSAS alone, and 7% of those with neither condition.

Service members with both conditions also were less likely to adhere to therapy; 30% regularly used continuous PAP therapy, compared with 55% of those who had OSAS alone.

And while continuous PAP therapy improved daytime sleepiness and quality of life in patients with both PTSD and OSAS, the degree of improvement was less than that experienced by those with OSAS alone. PTSD “represents an independent barrier to the effective treatment of OSAS and should prompt multipronged and individualized care,” they wrote.

The researchers reported having no financial disclosures.

The broad-spectrum triazole isavuconazole was as effective as voriconazole in patients with suspected invasive mold disease and caused significantly fewer drug-related adverse events, particularly those of the skin, eyes, and hepatobiliary system, a randomized double-blind study of 516 adults has shown.

The findings suggest that the newer agent “could allow safer therapy” for the primary treatment of invasive aspergillosis and other mold disease than standard therapy with voriconazole, researchers for the phase III, industry-sponsored SECURE trial say in a report published in the Lancet.

Wikimedia Commons

The researchers assessed the safety and efficacy of isavuconazole versus voriconazole in patients with invasive mold infection. Patients were recruited from 102 centers across 26 countries over a 7-year period and were randomized to receive either drug.

In the study group of 516 adults with suspected invasive mold infection who received at least one dose of either antifungal drug, isavuconazole proved to be noninferior to voriconazole, by the primary endpoint of all-cause mortality at 6 weeks.

All-cause mortality at 6 weeks in this intention-to-treat group, of whom more than 80% had hematologic malignant disease, was 19% in the isavuconazole group (48 of 258) and 20% (52 of 258) in the voriconazole group.

This primary endpoint was chosen because “it provides the most objective and reproducible effect of therapy, and approximates best the attributable mortality, because deaths due to competing causes occur increasingly after 6 weeks,” Dr. Johan A. Maertensof the UZ Leuven (Belgium), and his associates wrote.

Secondary endpoints included overall response at the end of treatment among patients who were determined by an independent review committee to have proven or probable invasive mold disease – the study’s modified intention-to-treat population – as well as all-cause mortality at day 42 and day 84.

All-cause mortality in this modified intention-to-treat group, as well as in the group of patients found to have proven or probable invasive aspergillosis, specifically, supported the study’s primary findings (Lancet 2016 Feb:387:760-9).

Nearly all patients in the study had at least one treatment-emergent adverse event, and the proportion with serious treatment-emergent adverse events was similar between the treatment groups. However, patients treated with isavuconazole had a significantly lower frequency of hepatobiliary disorders, eye disorders, and skin or subcutaneous disorders.

And overall, significantly fewer patients reported drug-related adverse events with isavuconazole (42% of patients) than with voriconazole (60% of patients). Discontinuation from adverse events, moreover, was significantly less common among isavuconazole-treated patients.

Of the 516 patients in the intention-to-treat group, approximately 53% were confirmed to have proven or probable invasive mold disease, and more than 80% of the mycologically documented cases were Aspergillus infections. Enrollment of patients with possible invasive mold disease at the start “reflects the real-life strategy of early initiation of antifungal treatment,” the investigators say.

Isavuconazonium sulfate was approved in 2015 by the FDA for the treatment of invasive aspergillosis and invasive mucormycosis.

Voriconazole is the current gold standard for the primary treatment of invasive aspergillosis and is recommended for some other mold infections as well, but it is not active against mucormycosis and has “highly variable nonlinear pharmacokinetics in adults,” which has triggered recommendations for drug monitoring, Dr. Maertens and his associates say.

Therapeutic monitoring aimed at individualizing dosage regimes in order to improve response and prevent adverse events became the standard of care in some institutions during the study period (2007-2013). The study used the labeled dose of voriconazole, however, and did not address the efficacy of either drug with therapeutic drug monitoring.

The study also excluded patients with AIDS, abnormal liver or renal function, and those receiving antifungal prophylaxis with a mold-active triazole – factors that may limit generalizability of the findings, the investigators note.

Funding for the study was provided by Astellas Pharma Global Development and Basilea Pharmaceutica International.

Dr. Maertens disclosed receiving grants and fees from Bio-Rad, personal fees and nonfinancial support from Astellas and Basilea, and grants, fees and support from Gilead Sciences, Merck Sharp and Dohme, and Pfizer during the study.

The broad-spectrum triazole isavuconazole was as effective as voriconazole in patients with suspected invasive mold disease and caused significantly fewer drug-related adverse events, particularly those of the skin, eyes, and hepatobiliary system, a randomized double-blind study of 516 adults has shown.

The findings suggest that the newer agent “could allow safer therapy” for the primary treatment of invasive aspergillosis and other mold disease than standard therapy with voriconazole, researchers for the phase III, industry-sponsored SECURE trial say in a report published in the Lancet.

Wikimedia Commons

The researchers assessed the safety and efficacy of isavuconazole versus voriconazole in patients with invasive mold infection. Patients were recruited from 102 centers across 26 countries over a 7-year period and were randomized to receive either drug.

In the study group of 516 adults with suspected invasive mold infection who received at least one dose of either antifungal drug, isavuconazole proved to be noninferior to voriconazole, by the primary endpoint of all-cause mortality at 6 weeks.

All-cause mortality at 6 weeks in this intention-to-treat group, of whom more than 80% had hematologic malignant disease, was 19% in the isavuconazole group (48 of 258) and 20% (52 of 258) in the voriconazole group.

This primary endpoint was chosen because “it provides the most objective and reproducible effect of therapy, and approximates best the attributable mortality, because deaths due to competing causes occur increasingly after 6 weeks,” Dr. Johan A. Maertensof the UZ Leuven (Belgium), and his associates wrote.

Secondary endpoints included overall response at the end of treatment among patients who were determined by an independent review committee to have proven or probable invasive mold disease – the study’s modified intention-to-treat population – as well as all-cause mortality at day 42 and day 84.

All-cause mortality in this modified intention-to-treat group, as well as in the group of patients found to have proven or probable invasive aspergillosis, specifically, supported the study’s primary findings (Lancet 2016 Feb:387:760-9).

Nearly all patients in the study had at least one treatment-emergent adverse event, and the proportion with serious treatment-emergent adverse events was similar between the treatment groups. However, patients treated with isavuconazole had a significantly lower frequency of hepatobiliary disorders, eye disorders, and skin or subcutaneous disorders.

And overall, significantly fewer patients reported drug-related adverse events with isavuconazole (42% of patients) than with voriconazole (60% of patients). Discontinuation from adverse events, moreover, was significantly less common among isavuconazole-treated patients.

Of the 516 patients in the intention-to-treat group, approximately 53% were confirmed to have proven or probable invasive mold disease, and more than 80% of the mycologically documented cases were Aspergillus infections. Enrollment of patients with possible invasive mold disease at the start “reflects the real-life strategy of early initiation of antifungal treatment,” the investigators say.

Isavuconazonium sulfate was approved in 2015 by the FDA for the treatment of invasive aspergillosis and invasive mucormycosis.

Voriconazole is the current gold standard for the primary treatment of invasive aspergillosis and is recommended for some other mold infections as well, but it is not active against mucormycosis and has “highly variable nonlinear pharmacokinetics in adults,” which has triggered recommendations for drug monitoring, Dr. Maertens and his associates say.

Therapeutic monitoring aimed at individualizing dosage regimes in order to improve response and prevent adverse events became the standard of care in some institutions during the study period (2007-2013). The study used the labeled dose of voriconazole, however, and did not address the efficacy of either drug with therapeutic drug monitoring.

The study also excluded patients with AIDS, abnormal liver or renal function, and those receiving antifungal prophylaxis with a mold-active triazole – factors that may limit generalizability of the findings, the investigators note.

Funding for the study was provided by Astellas Pharma Global Development and Basilea Pharmaceutica International.

Dr. Maertens disclosed receiving grants and fees from Bio-Rad, personal fees and nonfinancial support from Astellas and Basilea, and grants, fees and support from Gilead Sciences, Merck Sharp and Dohme, and Pfizer during the study.

The broad-spectrum triazole isavuconazole was as effective as voriconazole in patients with suspected invasive mold disease and caused significantly fewer drug-related adverse events, particularly those of the skin, eyes, and hepatobiliary system, a randomized double-blind study of 516 adults has shown.

The findings suggest that the newer agent “could allow safer therapy” for the primary treatment of invasive aspergillosis and other mold disease than standard therapy with voriconazole, researchers for the phase III, industry-sponsored SECURE trial say in a report published in the Lancet.

Wikimedia Commons

The researchers assessed the safety and efficacy of isavuconazole versus voriconazole in patients with invasive mold infection. Patients were recruited from 102 centers across 26 countries over a 7-year period and were randomized to receive either drug.

In the study group of 516 adults with suspected invasive mold infection who received at least one dose of either antifungal drug, isavuconazole proved to be noninferior to voriconazole, by the primary endpoint of all-cause mortality at 6 weeks.

All-cause mortality at 6 weeks in this intention-to-treat group, of whom more than 80% had hematologic malignant disease, was 19% in the isavuconazole group (48 of 258) and 20% (52 of 258) in the voriconazole group.

This primary endpoint was chosen because “it provides the most objective and reproducible effect of therapy, and approximates best the attributable mortality, because deaths due to competing causes occur increasingly after 6 weeks,” Dr. Johan A. Maertensof the UZ Leuven (Belgium), and his associates wrote.

Secondary endpoints included overall response at the end of treatment among patients who were determined by an independent review committee to have proven or probable invasive mold disease – the study’s modified intention-to-treat population – as well as all-cause mortality at day 42 and day 84.

All-cause mortality in this modified intention-to-treat group, as well as in the group of patients found to have proven or probable invasive aspergillosis, specifically, supported the study’s primary findings (Lancet 2016 Feb:387:760-9).

Nearly all patients in the study had at least one treatment-emergent adverse event, and the proportion with serious treatment-emergent adverse events was similar between the treatment groups. However, patients treated with isavuconazole had a significantly lower frequency of hepatobiliary disorders, eye disorders, and skin or subcutaneous disorders.

And overall, significantly fewer patients reported drug-related adverse events with isavuconazole (42% of patients) than with voriconazole (60% of patients). Discontinuation from adverse events, moreover, was significantly less common among isavuconazole-treated patients.

Of the 516 patients in the intention-to-treat group, approximately 53% were confirmed to have proven or probable invasive mold disease, and more than 80% of the mycologically documented cases were Aspergillus infections. Enrollment of patients with possible invasive mold disease at the start “reflects the real-life strategy of early initiation of antifungal treatment,” the investigators say.

Isavuconazonium sulfate was approved in 2015 by the FDA for the treatment of invasive aspergillosis and invasive mucormycosis.

Voriconazole is the current gold standard for the primary treatment of invasive aspergillosis and is recommended for some other mold infections as well, but it is not active against mucormycosis and has “highly variable nonlinear pharmacokinetics in adults,” which has triggered recommendations for drug monitoring, Dr. Maertens and his associates say.

Therapeutic monitoring aimed at individualizing dosage regimes in order to improve response and prevent adverse events became the standard of care in some institutions during the study period (2007-2013). The study used the labeled dose of voriconazole, however, and did not address the efficacy of either drug with therapeutic drug monitoring.

The study also excluded patients with AIDS, abnormal liver or renal function, and those receiving antifungal prophylaxis with a mold-active triazole – factors that may limit generalizability of the findings, the investigators note.

Funding for the study was provided by Astellas Pharma Global Development and Basilea Pharmaceutica International.

Dr. Maertens disclosed receiving grants and fees from Bio-Rad, personal fees and nonfinancial support from Astellas and Basilea, and grants, fees and support from Gilead Sciences, Merck Sharp and Dohme, and Pfizer during the study.

The focus of treatment. CF is not limited to the classic picture of lung and pancreas destruction with subsequent loss of function. The underlying pathology can occur in body epithelial tissues from the intestinal lining to sweat glands. These tissues contain cystic fibrosis transmembrane conductance regulator (CFTR), a protein that allows for the transport of chloride across epithelial cell membranes.² In individuals homozygous for mutated CFTR genes, chloride transport can be impaired. In addition to regulating chloride transport, CFTR is part of a larger, complex interaction of ion transport proteins such as the epithelial sodium channel (ENaC) and others that regulate bicarbonate secretion.² Decreased chloride ion transport in mutant CFTR negatively affects the ion transport complex; the result is a higher-than-normal viscosity of secreted body fluids.

Reason for hope. It is this impairment of chloride ion transport that leads to the classic phenotypic features of CF (eg, pulmonary function decline, pancreatic insufficiency, malnutrition, chronic respiratory infection), and is the target of both established and emerging therapies³—both of which I will review here.

For 90% of adults with cystic fibrosis, sweat chloride will be in the abnormal range of >60 mmol/L.

When to consider a CF diagnosis

Cystic fibrosis remains a clinical diagnosis when evidence of at least one phenotypic feature of the disease (TABLE 1) exists in the presence of laboratory evidence of a CFTR abnormality.⁴ Confirmation of CFTR dysfunction is demonstrated by an abnormality on sweat testing or identification of a CF-causing mutation in each copy of CFTR (ie, one on each chromosome).⁵ All 50 states now have neonatal laboratory screening programs;⁴ despite this, 30% of cases in 2012 were still diagnosed in those older than 1 year of age, with 3% to 5% diagnosed after age 18.¹

A sweat chloride reading in the abnormal range (>60 mmol/L) is present in 90% of patients diagnosed with CF in adulthood; this test remains the gold standard in the diagnosis of CF and the initial test of choice in suspected cases.⁴ Newborn screening programs identify those at risk by detecting persistent hypertrypsinogenemia and referring those with positive results for definitive testing with sweat chloride evaluation. Keep CF in mind when evaluating adolescents and adults who have chronic sinusitis, chronic/recurrent pulmonary infections, chronic/recurrent pancreatitis, or infertility from absence of the vas deferens.⁴ When features of the CF phenotype are present, especially if there is a known positive family history of CF or CF carrier status, order sweat chloride testing.

Traditional therapies

Both maintenance and acute therapies are directed throughout the body at decreasing fluid viscosity, clearing fluid with a high viscosity, or treating the tissue destruction that results from highly-viscous fluid.³ The traditional classic picture of CF is one of lung and pancreas destruction with subsequent loss of function. However, CF is, in reality, a full-body disease.

Respiratory system: Lungs

CFTR dysfunction in the lungs results in thick pulmonary secretions as the aqueous surface layer (ASL) lining the alveolar epithelium becomes dehydrated and creates a prime environment for the development of chronic infection. What ensues is a recurrent cycle of chronic infection, inflammation, and tissue destruction with loss of lung volume and function. Current therapies interrupt this cycle at multiple points.⁶

Airway clearance is one of the hallmarks of CF therapy, using both chemical and mechanical treatments. Daily, most patients will use either a therapy vest that administers sheering forces to the chest cavity or an airflow device that creates positive expiratory pressure and laminar flow to aid in expectorating pulmonary secretions.⁷ Because exercise has yielded comparable results to mechanical or airflow clearance devices, it is recommended that all CF patients who are not otherwise prohibited engage in regular, vigorous exercise in accordance with standard recommendations for the general public.⁷

Mechanical therapies are often preceded by airway dilation with short- and long-acting bronchodilators and inhaled steroids that open airways for optimal airway clearance.⁴ Thick secretions can be treated directly and enzymatically with nebulized dornase alpha,^4,8 which is also best administered before mechanical clearance therapy. Finally, viscosity of airway secretions can be decreased by improving the hydration of the ASL with nebulized 7% hypertonic saline.^4,8

Infection suppression. Thickened pulmonary secretions create a fertile environment for the development of chronic infection. By the time most CF patients reach adulthood, many are colonized with mucoid producing strains of Pseudomonas aeruginosa.^4,8-10 Many may also have chronic infection with Staphylococcus aureus, some strains of which may be methicillin-resistant. Quarterly culture and sensitivity results can be essential in directing acute antibiotic therapy, both in the hospital and ambulatory settings. In addition, in the case of Pseudomonas, inhaled antibiotics suppress chronic infection, improve lung function, decrease pulmonary secretions, and reduce inflammation.

Formulations are available for tobramycin and aztreonam, both of which are administered every other month to reduce toxicities and to deter antibiotic resistance. Some patients may use a single agent or may alternate agents every month. When acute antibiotic therapy is necessary for a pulmonary exacerbation, the inhaled agent is generally withheld. If outpatient treatment is warranted, the only available oral antibiotics with anti-pseudomonal activity are ciprofloxacin and levofloxacin.^4,8-10S aureus can be treated with trimethoprim/sulfamethoxazole or doxycycline.^4,8-10

Inflammation reduction is addressed with high-dose ibuprofen twice daily, azithromycin daily or 3 times weekly, or both. Children up to age 18 benefit from ibuprofen, which also improves forced expiratory volume in one second (FEV₁) to a greater extent than azithromycin.⁸ Adults, however, face the risk of gastrointestinal bleeding and renal dysfunction with ibuprofen, which must be weighed against its potential anti-inflammatory benefit. Both populations, however, benefit from chronic azithromycin, whose mechanism of action in this setting is believed to be more anti-inflammatory than bacterial suppression, since it has no direct bactericidal effect on the primary colonizing microbe, P aeruginosa.^4,11

Gastrointestinal system: Pancreas

Cystic fibrosis was first comprehensively described in 1938 and was named for the diseased appearance of the pancreas.¹² As happens in the lungs, thick pancreatic duct secretions create a cycle of tissue destruction, inflammation, and dysfunction.² CF patients lack adequate secretion of pancreatic enzymes and bicarbonate into the small bowel, which progressively leads to pancreatic dysfunction in most patients.

As malabsorption of nutrients advances, patients suffer varying degrees of malnutrition and vitamin deficiency, especially of the fat-soluble vitamins A, D, E, and K. Over 85% of CF patients have deficient pancreatic function, requiring pancreatic enzyme supplementation with all food intake and daily vitamin supplementation.²

Because exercise has yielded comparable results to mechanical or airflow clearance devices, CF patients should engage in regular, vigorous exercise.

Ensuring adequate nutrition. Most CF patients experience a chronic mismatch of dietary intake against caloric expenditure and benefit from aggressive nutritional management featuring a high-calorie diet with supplementation in the form of nutrition shakes or bars.² There is a well-documented linear relationship between BMI and FEV₁. Lung function declines in CF when a man’s body mass index (BMI) falls below 23 kg/m² and a woman’s BMI drops below 22 kg/m².² For this reason, the goal for caloric intake can be as high as 200% of the customary recommended daily allowance.²

Watch for CF-related diabetes. Since the pancreas is also the major source of endogenous insulin, nearly half of adults with CF will develop cystic fibrosis-related diabetes (CFRD) as pancreatic deficiency progresses.¹³ Similar to the relationship between BMI and FEV₁, there is a relationship between glucose intolerance and FEV₁. For this reason, annual diabetes screening is recommended for all CF patients ages 10 years and older.¹³ Because glycated hemoglobin (HbA1c) may not accurately reflect low levels of glucose intolerance, screen for CFRD with a 2-hour 75-g oral glucose tolerance test.¹³ Early insulin therapy can help maintain BMI and lower average blood sugar in support of FEV₁. Once CFRD is diagnosed, the goals and recommendations for control are largely the same as those recommended by the American Diabetes Association for other forms of diabetes.¹³

Gastrointestinal system: Alimentary canal

CF is often mistakenly believed to be primarily a pulmonary disease since 85% of the mortality is due to lung dysfunction,⁷ but intermittent abdominal pain is a common experience for most patients, and disorders can range from gastroesophageal reflux disease (GERD) to small bowel bacterial overgrowth (SBBO) to constipation. Up to 85% of adult patients experience symptoms of reflux, with as many as 40% of cases occurring silently.² Proton pump inhibitors are a first-line treatment, but they can also contribute to intestinal bacterial overgrowth and pulmonary infections.

In SBBO, gram-negative colonic bacteria colonize the small bowel and can contribute to abdominal pain and malabsorption, weight loss, and malnutrition. Treatment requires antibiotics with activity against gram-negative organisms, or non-absorbable agents such as rifamyxin, sometimes on a chronic, recurrent, or rotating basis.²

Chronic constipation is also quite common among CF patients and many require daily administration of poly-ethylene-glycol. Before newborn screening programs were introduced, infants would on occasion present with complete distal intestinal obstruction. Adults are not immune to obstructive complications and may require hospitalization for bowel cleansing.

Because HbA1c may not accurately reflect low levels of glucose intolerance, screen for CF-related diabetes with a 2-hour 75-g oral glucose tolerance test.

Gastrointestinal system: Liver

Liver disease is relatively common in CF, with up to 24% of adults experiencing hepatomegaly or persistently elevated liver function tests (LFT).⁴ Progressive biliary fibrosis and cirrhosis are encountered more often as the median survival age has increased. There is evidence that ursodeoxycholic acid (UDCA) can be a useful adjunct in the treatment of cholestasis, but it is not clear if it alters mortality or progression to cirrhosis. Only CF patients with elevated LFTs should be started on UDCA.⁴

Other areas of concern: Sinuses, serum sodium levels

Chronic, symptomatic sinus disease in CF patients—chiefly polyposis—is common and may require repeat surgery, although most patients with extensive nasal polyps find symptom relief with daily sinus rinses. Intranasal steroids and intranasal antibiotics are also often employed, and many CF patients need to be in regular contact with an otolaryngologist.¹⁴ For symptoms of allergic rhinitis, recommend OTC antihistamines in standard dosages.

Exercise is recommended for all CF patients, as noted earlier, and as life expectancy increases, many are engaging in more strenuous and longer duration activities.¹⁵ Due to high sweat sodium loss, CF patients are at risk for hyponatremia, especially when exercising on days with high temperatures and humidity. CF patients need to replace sodium losses in these conditions and when exercising for extended periods.

There are no evidence-based guidelines for sodium replacement. The Cystic Fibrosis Foundation (CFF) recommends that patients increase salt in the diet when under conditions likely to result in increased sodium loss, such as exercise. It has been thought that CF patients can easily dehydrate due to an impaired thirst mechanism and, when exercising, should consume fluids beyond the need to quench thirst.^16,17 More recent evidence suggests, however, that the thirst mechanism in those with CF remains normally intact and that overconsumption of fluids beyond the level of thirst may predispose the individual to exercise-associated hyponatremia as serum sodium is diluted.¹⁵

For Pseudomonas aeruginosa infection, inhaled antibiotics suppress chronic infection, improve lung function, decrease pulmonary secretions, and reduce inflammation.

New therapies

Small-molecule CFTR-modulating compounds are a promising development in the treatment of CF. The first such available medication was ivacaftor in 2012. Because these molecules are mutation specific, ivacaftor was available at first only for patients with at least one copy of the G551D mutation,¹⁸ which means about 5% of patients with CF.³

Ivacaftor increases the likelihood that the CFTR chloride channel will open and patients will exhibit a reduction in sweat chloride levels. In the first reported clinical trial of ivacaftor involving patients with the G551D mutation, FEV₁ improvements of 10% occurred by the second week of therapy and persisted for 48 weeks.¹⁸ The drug has now been approved by the US Food and Drug Administration (FDA) for patients 12 years of age and older with at least one of the following mutations: R117H, G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D.¹⁹

A medication combining ivacaftor with lumacaftor is also now available for patients with a copy of F508del on both chromosomes. F508del is the most common CFTR mutation, with one copy present in almost 87% of people with CF in the United States.¹ Since 47% of CF patients have 2 copies of F508del,¹ about half of those with CF in the United States are now eligible for small-molecule therapy. Lumacaftor acts by facilitating transport of a misfolded CFTR to the cell membrane where ivacaftor then increases the probability of an open chloride channel. This combination medication has improved lung function by about 5%.

The ivacaftor/lumacaftor combination was approved by the FDA in July 2015. Both ivacaftor and the ivacaftor/lumacaftor combination were deemed by the FDA to demonstrate statistically significant and sustained FEV₁ improvements over placebo.

The CFF was instrumental in providing financial support for the development of both ivacaftor and the ivacaftor/lumacaftor combination and continues to provide significant research advancement. According to the CFF (www.cff.org), medications currently in the development pipeline include compounds that provide CFTR modulation, surface airway liquid restoration, anti-inflammation, inhaled anti-infection, and pancreatic enzyme function. For more on CFF, see "The traditional CF care model.”^4,20

CORRESPONDENCE
Douglas Lewis, MD, 1121 S. Clifton, Wichita, KS 67218; [email protected].

The focus of treatment. CF is not limited to the classic picture of lung and pancreas destruction with subsequent loss of function. The underlying pathology can occur in body epithelial tissues from the intestinal lining to sweat glands. These tissues contain cystic fibrosis transmembrane conductance regulator (CFTR), a protein that allows for the transport of chloride across epithelial cell membranes.² In individuals homozygous for mutated CFTR genes, chloride transport can be impaired. In addition to regulating chloride transport, CFTR is part of a larger, complex interaction of ion transport proteins such as the epithelial sodium channel (ENaC) and others that regulate bicarbonate secretion.² Decreased chloride ion transport in mutant CFTR negatively affects the ion transport complex; the result is a higher-than-normal viscosity of secreted body fluids.

Reason for hope. It is this impairment of chloride ion transport that leads to the classic phenotypic features of CF (eg, pulmonary function decline, pancreatic insufficiency, malnutrition, chronic respiratory infection), and is the target of both established and emerging therapies³—both of which I will review here.

For 90% of adults with cystic fibrosis, sweat chloride will be in the abnormal range of >60 mmol/L.

When to consider a CF diagnosis

Cystic fibrosis remains a clinical diagnosis when evidence of at least one phenotypic feature of the disease (TABLE 1) exists in the presence of laboratory evidence of a CFTR abnormality.⁴ Confirmation of CFTR dysfunction is demonstrated by an abnormality on sweat testing or identification of a CF-causing mutation in each copy of CFTR (ie, one on each chromosome).⁵ All 50 states now have neonatal laboratory screening programs;⁴ despite this, 30% of cases in 2012 were still diagnosed in those older than 1 year of age, with 3% to 5% diagnosed after age 18.¹

A sweat chloride reading in the abnormal range (>60 mmol/L) is present in 90% of patients diagnosed with CF in adulthood; this test remains the gold standard in the diagnosis of CF and the initial test of choice in suspected cases.⁴ Newborn screening programs identify those at risk by detecting persistent hypertrypsinogenemia and referring those with positive results for definitive testing with sweat chloride evaluation. Keep CF in mind when evaluating adolescents and adults who have chronic sinusitis, chronic/recurrent pulmonary infections, chronic/recurrent pancreatitis, or infertility from absence of the vas deferens.⁴ When features of the CF phenotype are present, especially if there is a known positive family history of CF or CF carrier status, order sweat chloride testing.

Traditional therapies

Both maintenance and acute therapies are directed throughout the body at decreasing fluid viscosity, clearing fluid with a high viscosity, or treating the tissue destruction that results from highly-viscous fluid.³ The traditional classic picture of CF is one of lung and pancreas destruction with subsequent loss of function. However, CF is, in reality, a full-body disease.

Respiratory system: Lungs

CFTR dysfunction in the lungs results in thick pulmonary secretions as the aqueous surface layer (ASL) lining the alveolar epithelium becomes dehydrated and creates a prime environment for the development of chronic infection. What ensues is a recurrent cycle of chronic infection, inflammation, and tissue destruction with loss of lung volume and function. Current therapies interrupt this cycle at multiple points.⁶

Airway clearance is one of the hallmarks of CF therapy, using both chemical and mechanical treatments. Daily, most patients will use either a therapy vest that administers sheering forces to the chest cavity or an airflow device that creates positive expiratory pressure and laminar flow to aid in expectorating pulmonary secretions.⁷ Because exercise has yielded comparable results to mechanical or airflow clearance devices, it is recommended that all CF patients who are not otherwise prohibited engage in regular, vigorous exercise in accordance with standard recommendations for the general public.⁷

Mechanical therapies are often preceded by airway dilation with short- and long-acting bronchodilators and inhaled steroids that open airways for optimal airway clearance.⁴ Thick secretions can be treated directly and enzymatically with nebulized dornase alpha,^4,8 which is also best administered before mechanical clearance therapy. Finally, viscosity of airway secretions can be decreased by improving the hydration of the ASL with nebulized 7% hypertonic saline.^4,8

Infection suppression. Thickened pulmonary secretions create a fertile environment for the development of chronic infection. By the time most CF patients reach adulthood, many are colonized with mucoid producing strains of Pseudomonas aeruginosa.^4,8-10 Many may also have chronic infection with Staphylococcus aureus, some strains of which may be methicillin-resistant. Quarterly culture and sensitivity results can be essential in directing acute antibiotic therapy, both in the hospital and ambulatory settings. In addition, in the case of Pseudomonas, inhaled antibiotics suppress chronic infection, improve lung function, decrease pulmonary secretions, and reduce inflammation.

Formulations are available for tobramycin and aztreonam, both of which are administered every other month to reduce toxicities and to deter antibiotic resistance. Some patients may use a single agent or may alternate agents every month. When acute antibiotic therapy is necessary for a pulmonary exacerbation, the inhaled agent is generally withheld. If outpatient treatment is warranted, the only available oral antibiotics with anti-pseudomonal activity are ciprofloxacin and levofloxacin.^4,8-10S aureus can be treated with trimethoprim/sulfamethoxazole or doxycycline.^4,8-10

Inflammation reduction is addressed with high-dose ibuprofen twice daily, azithromycin daily or 3 times weekly, or both. Children up to age 18 benefit from ibuprofen, which also improves forced expiratory volume in one second (FEV₁) to a greater extent than azithromycin.⁸ Adults, however, face the risk of gastrointestinal bleeding and renal dysfunction with ibuprofen, which must be weighed against its potential anti-inflammatory benefit. Both populations, however, benefit from chronic azithromycin, whose mechanism of action in this setting is believed to be more anti-inflammatory than bacterial suppression, since it has no direct bactericidal effect on the primary colonizing microbe, P aeruginosa.^4,11

Gastrointestinal system: Pancreas

Cystic fibrosis was first comprehensively described in 1938 and was named for the diseased appearance of the pancreas.¹² As happens in the lungs, thick pancreatic duct secretions create a cycle of tissue destruction, inflammation, and dysfunction.² CF patients lack adequate secretion of pancreatic enzymes and bicarbonate into the small bowel, which progressively leads to pancreatic dysfunction in most patients.

As malabsorption of nutrients advances, patients suffer varying degrees of malnutrition and vitamin deficiency, especially of the fat-soluble vitamins A, D, E, and K. Over 85% of CF patients have deficient pancreatic function, requiring pancreatic enzyme supplementation with all food intake and daily vitamin supplementation.²

Because exercise has yielded comparable results to mechanical or airflow clearance devices, CF patients should engage in regular, vigorous exercise.

Ensuring adequate nutrition. Most CF patients experience a chronic mismatch of dietary intake against caloric expenditure and benefit from aggressive nutritional management featuring a high-calorie diet with supplementation in the form of nutrition shakes or bars.² There is a well-documented linear relationship between BMI and FEV₁. Lung function declines in CF when a man’s body mass index (BMI) falls below 23 kg/m² and a woman’s BMI drops below 22 kg/m².² For this reason, the goal for caloric intake can be as high as 200% of the customary recommended daily allowance.²

Watch for CF-related diabetes. Since the pancreas is also the major source of endogenous insulin, nearly half of adults with CF will develop cystic fibrosis-related diabetes (CFRD) as pancreatic deficiency progresses.¹³ Similar to the relationship between BMI and FEV₁, there is a relationship between glucose intolerance and FEV₁. For this reason, annual diabetes screening is recommended for all CF patients ages 10 years and older.¹³ Because glycated hemoglobin (HbA1c) may not accurately reflect low levels of glucose intolerance, screen for CFRD with a 2-hour 75-g oral glucose tolerance test.¹³ Early insulin therapy can help maintain BMI and lower average blood sugar in support of FEV₁. Once CFRD is diagnosed, the goals and recommendations for control are largely the same as those recommended by the American Diabetes Association for other forms of diabetes.¹³

Gastrointestinal system: Alimentary canal

CF is often mistakenly believed to be primarily a pulmonary disease since 85% of the mortality is due to lung dysfunction,⁷ but intermittent abdominal pain is a common experience for most patients, and disorders can range from gastroesophageal reflux disease (GERD) to small bowel bacterial overgrowth (SBBO) to constipation. Up to 85% of adult patients experience symptoms of reflux, with as many as 40% of cases occurring silently.² Proton pump inhibitors are a first-line treatment, but they can also contribute to intestinal bacterial overgrowth and pulmonary infections.

In SBBO, gram-negative colonic bacteria colonize the small bowel and can contribute to abdominal pain and malabsorption, weight loss, and malnutrition. Treatment requires antibiotics with activity against gram-negative organisms, or non-absorbable agents such as rifamyxin, sometimes on a chronic, recurrent, or rotating basis.²

Chronic constipation is also quite common among CF patients and many require daily administration of poly-ethylene-glycol. Before newborn screening programs were introduced, infants would on occasion present with complete distal intestinal obstruction. Adults are not immune to obstructive complications and may require hospitalization for bowel cleansing.

Because HbA1c may not accurately reflect low levels of glucose intolerance, screen for CF-related diabetes with a 2-hour 75-g oral glucose tolerance test.

Gastrointestinal system: Liver

Liver disease is relatively common in CF, with up to 24% of adults experiencing hepatomegaly or persistently elevated liver function tests (LFT).⁴ Progressive biliary fibrosis and cirrhosis are encountered more often as the median survival age has increased. There is evidence that ursodeoxycholic acid (UDCA) can be a useful adjunct in the treatment of cholestasis, but it is not clear if it alters mortality or progression to cirrhosis. Only CF patients with elevated LFTs should be started on UDCA.⁴

Other areas of concern: Sinuses, serum sodium levels

Chronic, symptomatic sinus disease in CF patients—chiefly polyposis—is common and may require repeat surgery, although most patients with extensive nasal polyps find symptom relief with daily sinus rinses. Intranasal steroids and intranasal antibiotics are also often employed, and many CF patients need to be in regular contact with an otolaryngologist.¹⁴ For symptoms of allergic rhinitis, recommend OTC antihistamines in standard dosages.

Exercise is recommended for all CF patients, as noted earlier, and as life expectancy increases, many are engaging in more strenuous and longer duration activities.¹⁵ Due to high sweat sodium loss, CF patients are at risk for hyponatremia, especially when exercising on days with high temperatures and humidity. CF patients need to replace sodium losses in these conditions and when exercising for extended periods.

There are no evidence-based guidelines for sodium replacement. The Cystic Fibrosis Foundation (CFF) recommends that patients increase salt in the diet when under conditions likely to result in increased sodium loss, such as exercise. It has been thought that CF patients can easily dehydrate due to an impaired thirst mechanism and, when exercising, should consume fluids beyond the need to quench thirst.^16,17 More recent evidence suggests, however, that the thirst mechanism in those with CF remains normally intact and that overconsumption of fluids beyond the level of thirst may predispose the individual to exercise-associated hyponatremia as serum sodium is diluted.¹⁵

For Pseudomonas aeruginosa infection, inhaled antibiotics suppress chronic infection, improve lung function, decrease pulmonary secretions, and reduce inflammation.

New therapies

Small-molecule CFTR-modulating compounds are a promising development in the treatment of CF. The first such available medication was ivacaftor in 2012. Because these molecules are mutation specific, ivacaftor was available at first only for patients with at least one copy of the G551D mutation,¹⁸ which means about 5% of patients with CF.³

Ivacaftor increases the likelihood that the CFTR chloride channel will open and patients will exhibit a reduction in sweat chloride levels. In the first reported clinical trial of ivacaftor involving patients with the G551D mutation, FEV₁ improvements of 10% occurred by the second week of therapy and persisted for 48 weeks.¹⁸ The drug has now been approved by the US Food and Drug Administration (FDA) for patients 12 years of age and older with at least one of the following mutations: R117H, G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D.¹⁹

A medication combining ivacaftor with lumacaftor is also now available for patients with a copy of F508del on both chromosomes. F508del is the most common CFTR mutation, with one copy present in almost 87% of people with CF in the United States.¹ Since 47% of CF patients have 2 copies of F508del,¹ about half of those with CF in the United States are now eligible for small-molecule therapy. Lumacaftor acts by facilitating transport of a misfolded CFTR to the cell membrane where ivacaftor then increases the probability of an open chloride channel. This combination medication has improved lung function by about 5%.

The ivacaftor/lumacaftor combination was approved by the FDA in July 2015. Both ivacaftor and the ivacaftor/lumacaftor combination were deemed by the FDA to demonstrate statistically significant and sustained FEV₁ improvements over placebo.

The CFF was instrumental in providing financial support for the development of both ivacaftor and the ivacaftor/lumacaftor combination and continues to provide significant research advancement. According to the CFF (www.cff.org), medications currently in the development pipeline include compounds that provide CFTR modulation, surface airway liquid restoration, anti-inflammation, inhaled anti-infection, and pancreatic enzyme function. For more on CFF, see "The traditional CF care model.”^4,20

CORRESPONDENCE
Douglas Lewis, MD, 1121 S. Clifton, Wichita, KS 67218; [email protected].

The focus of treatment. CF is not limited to the classic picture of lung and pancreas destruction with subsequent loss of function. The underlying pathology can occur in body epithelial tissues from the intestinal lining to sweat glands. These tissues contain cystic fibrosis transmembrane conductance regulator (CFTR), a protein that allows for the transport of chloride across epithelial cell membranes.² In individuals homozygous for mutated CFTR genes, chloride transport can be impaired. In addition to regulating chloride transport, CFTR is part of a larger, complex interaction of ion transport proteins such as the epithelial sodium channel (ENaC) and others that regulate bicarbonate secretion.² Decreased chloride ion transport in mutant CFTR negatively affects the ion transport complex; the result is a higher-than-normal viscosity of secreted body fluids.

Reason for hope. It is this impairment of chloride ion transport that leads to the classic phenotypic features of CF (eg, pulmonary function decline, pancreatic insufficiency, malnutrition, chronic respiratory infection), and is the target of both established and emerging therapies³—both of which I will review here.

For 90% of adults with cystic fibrosis, sweat chloride will be in the abnormal range of >60 mmol/L.

When to consider a CF diagnosis

Cystic fibrosis remains a clinical diagnosis when evidence of at least one phenotypic feature of the disease (TABLE 1) exists in the presence of laboratory evidence of a CFTR abnormality.⁴ Confirmation of CFTR dysfunction is demonstrated by an abnormality on sweat testing or identification of a CF-causing mutation in each copy of CFTR (ie, one on each chromosome).⁵ All 50 states now have neonatal laboratory screening programs;⁴ despite this, 30% of cases in 2012 were still diagnosed in those older than 1 year of age, with 3% to 5% diagnosed after age 18.¹

A sweat chloride reading in the abnormal range (>60 mmol/L) is present in 90% of patients diagnosed with CF in adulthood; this test remains the gold standard in the diagnosis of CF and the initial test of choice in suspected cases.⁴ Newborn screening programs identify those at risk by detecting persistent hypertrypsinogenemia and referring those with positive results for definitive testing with sweat chloride evaluation. Keep CF in mind when evaluating adolescents and adults who have chronic sinusitis, chronic/recurrent pulmonary infections, chronic/recurrent pancreatitis, or infertility from absence of the vas deferens.⁴ When features of the CF phenotype are present, especially if there is a known positive family history of CF or CF carrier status, order sweat chloride testing.

Traditional therapies

Both maintenance and acute therapies are directed throughout the body at decreasing fluid viscosity, clearing fluid with a high viscosity, or treating the tissue destruction that results from highly-viscous fluid.³ The traditional classic picture of CF is one of lung and pancreas destruction with subsequent loss of function. However, CF is, in reality, a full-body disease.

Respiratory system: Lungs

CFTR dysfunction in the lungs results in thick pulmonary secretions as the aqueous surface layer (ASL) lining the alveolar epithelium becomes dehydrated and creates a prime environment for the development of chronic infection. What ensues is a recurrent cycle of chronic infection, inflammation, and tissue destruction with loss of lung volume and function. Current therapies interrupt this cycle at multiple points.⁶

Airway clearance is one of the hallmarks of CF therapy, using both chemical and mechanical treatments. Daily, most patients will use either a therapy vest that administers sheering forces to the chest cavity or an airflow device that creates positive expiratory pressure and laminar flow to aid in expectorating pulmonary secretions.⁷ Because exercise has yielded comparable results to mechanical or airflow clearance devices, it is recommended that all CF patients who are not otherwise prohibited engage in regular, vigorous exercise in accordance with standard recommendations for the general public.⁷

Mechanical therapies are often preceded by airway dilation with short- and long-acting bronchodilators and inhaled steroids that open airways for optimal airway clearance.⁴ Thick secretions can be treated directly and enzymatically with nebulized dornase alpha,^4,8 which is also best administered before mechanical clearance therapy. Finally, viscosity of airway secretions can be decreased by improving the hydration of the ASL with nebulized 7% hypertonic saline.^4,8

Infection suppression. Thickened pulmonary secretions create a fertile environment for the development of chronic infection. By the time most CF patients reach adulthood, many are colonized with mucoid producing strains of Pseudomonas aeruginosa.^4,8-10 Many may also have chronic infection with Staphylococcus aureus, some strains of which may be methicillin-resistant. Quarterly culture and sensitivity results can be essential in directing acute antibiotic therapy, both in the hospital and ambulatory settings. In addition, in the case of Pseudomonas, inhaled antibiotics suppress chronic infection, improve lung function, decrease pulmonary secretions, and reduce inflammation.

Formulations are available for tobramycin and aztreonam, both of which are administered every other month to reduce toxicities and to deter antibiotic resistance. Some patients may use a single agent or may alternate agents every month. When acute antibiotic therapy is necessary for a pulmonary exacerbation, the inhaled agent is generally withheld. If outpatient treatment is warranted, the only available oral antibiotics with anti-pseudomonal activity are ciprofloxacin and levofloxacin.^4,8-10S aureus can be treated with trimethoprim/sulfamethoxazole or doxycycline.^4,8-10

Inflammation reduction is addressed with high-dose ibuprofen twice daily, azithromycin daily or 3 times weekly, or both. Children up to age 18 benefit from ibuprofen, which also improves forced expiratory volume in one second (FEV₁) to a greater extent than azithromycin.⁸ Adults, however, face the risk of gastrointestinal bleeding and renal dysfunction with ibuprofen, which must be weighed against its potential anti-inflammatory benefit. Both populations, however, benefit from chronic azithromycin, whose mechanism of action in this setting is believed to be more anti-inflammatory than bacterial suppression, since it has no direct bactericidal effect on the primary colonizing microbe, P aeruginosa.^4,11

Gastrointestinal system: Pancreas

Cystic fibrosis was first comprehensively described in 1938 and was named for the diseased appearance of the pancreas.¹² As happens in the lungs, thick pancreatic duct secretions create a cycle of tissue destruction, inflammation, and dysfunction.² CF patients lack adequate secretion of pancreatic enzymes and bicarbonate into the small bowel, which progressively leads to pancreatic dysfunction in most patients.

As malabsorption of nutrients advances, patients suffer varying degrees of malnutrition and vitamin deficiency, especially of the fat-soluble vitamins A, D, E, and K. Over 85% of CF patients have deficient pancreatic function, requiring pancreatic enzyme supplementation with all food intake and daily vitamin supplementation.²

Because exercise has yielded comparable results to mechanical or airflow clearance devices, CF patients should engage in regular, vigorous exercise.

Ensuring adequate nutrition. Most CF patients experience a chronic mismatch of dietary intake against caloric expenditure and benefit from aggressive nutritional management featuring a high-calorie diet with supplementation in the form of nutrition shakes or bars.² There is a well-documented linear relationship between BMI and FEV₁. Lung function declines in CF when a man’s body mass index (BMI) falls below 23 kg/m² and a woman’s BMI drops below 22 kg/m².² For this reason, the goal for caloric intake can be as high as 200% of the customary recommended daily allowance.²

Watch for CF-related diabetes. Since the pancreas is also the major source of endogenous insulin, nearly half of adults with CF will develop cystic fibrosis-related diabetes (CFRD) as pancreatic deficiency progresses.¹³ Similar to the relationship between BMI and FEV₁, there is a relationship between glucose intolerance and FEV₁. For this reason, annual diabetes screening is recommended for all CF patients ages 10 years and older.¹³ Because glycated hemoglobin (HbA1c) may not accurately reflect low levels of glucose intolerance, screen for CFRD with a 2-hour 75-g oral glucose tolerance test.¹³ Early insulin therapy can help maintain BMI and lower average blood sugar in support of FEV₁. Once CFRD is diagnosed, the goals and recommendations for control are largely the same as those recommended by the American Diabetes Association for other forms of diabetes.¹³

Gastrointestinal system: Alimentary canal

CF is often mistakenly believed to be primarily a pulmonary disease since 85% of the mortality is due to lung dysfunction,⁷ but intermittent abdominal pain is a common experience for most patients, and disorders can range from gastroesophageal reflux disease (GERD) to small bowel bacterial overgrowth (SBBO) to constipation. Up to 85% of adult patients experience symptoms of reflux, with as many as 40% of cases occurring silently.² Proton pump inhibitors are a first-line treatment, but they can also contribute to intestinal bacterial overgrowth and pulmonary infections.

In SBBO, gram-negative colonic bacteria colonize the small bowel and can contribute to abdominal pain and malabsorption, weight loss, and malnutrition. Treatment requires antibiotics with activity against gram-negative organisms, or non-absorbable agents such as rifamyxin, sometimes on a chronic, recurrent, or rotating basis.²

Chronic constipation is also quite common among CF patients and many require daily administration of poly-ethylene-glycol. Before newborn screening programs were introduced, infants would on occasion present with complete distal intestinal obstruction. Adults are not immune to obstructive complications and may require hospitalization for bowel cleansing.

Because HbA1c may not accurately reflect low levels of glucose intolerance, screen for CF-related diabetes with a 2-hour 75-g oral glucose tolerance test.

Gastrointestinal system: Liver

Liver disease is relatively common in CF, with up to 24% of adults experiencing hepatomegaly or persistently elevated liver function tests (LFT).⁴ Progressive biliary fibrosis and cirrhosis are encountered more often as the median survival age has increased. There is evidence that ursodeoxycholic acid (UDCA) can be a useful adjunct in the treatment of cholestasis, but it is not clear if it alters mortality or progression to cirrhosis. Only CF patients with elevated LFTs should be started on UDCA.⁴

Other areas of concern: Sinuses, serum sodium levels

Chronic, symptomatic sinus disease in CF patients—chiefly polyposis—is common and may require repeat surgery, although most patients with extensive nasal polyps find symptom relief with daily sinus rinses. Intranasal steroids and intranasal antibiotics are also often employed, and many CF patients need to be in regular contact with an otolaryngologist.¹⁴ For symptoms of allergic rhinitis, recommend OTC antihistamines in standard dosages.

Exercise is recommended for all CF patients, as noted earlier, and as life expectancy increases, many are engaging in more strenuous and longer duration activities.¹⁵ Due to high sweat sodium loss, CF patients are at risk for hyponatremia, especially when exercising on days with high temperatures and humidity. CF patients need to replace sodium losses in these conditions and when exercising for extended periods.

There are no evidence-based guidelines for sodium replacement. The Cystic Fibrosis Foundation (CFF) recommends that patients increase salt in the diet when under conditions likely to result in increased sodium loss, such as exercise. It has been thought that CF patients can easily dehydrate due to an impaired thirst mechanism and, when exercising, should consume fluids beyond the need to quench thirst.^16,17 More recent evidence suggests, however, that the thirst mechanism in those with CF remains normally intact and that overconsumption of fluids beyond the level of thirst may predispose the individual to exercise-associated hyponatremia as serum sodium is diluted.¹⁵

For Pseudomonas aeruginosa infection, inhaled antibiotics suppress chronic infection, improve lung function, decrease pulmonary secretions, and reduce inflammation.

New therapies

Small-molecule CFTR-modulating compounds are a promising development in the treatment of CF. The first such available medication was ivacaftor in 2012. Because these molecules are mutation specific, ivacaftor was available at first only for patients with at least one copy of the G551D mutation,¹⁸ which means about 5% of patients with CF.³

Ivacaftor increases the likelihood that the CFTR chloride channel will open and patients will exhibit a reduction in sweat chloride levels. In the first reported clinical trial of ivacaftor involving patients with the G551D mutation, FEV₁ improvements of 10% occurred by the second week of therapy and persisted for 48 weeks.¹⁸ The drug has now been approved by the US Food and Drug Administration (FDA) for patients 12 years of age and older with at least one of the following mutations: R117H, G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D.¹⁹

A medication combining ivacaftor with lumacaftor is also now available for patients with a copy of F508del on both chromosomes. F508del is the most common CFTR mutation, with one copy present in almost 87% of people with CF in the United States.¹ Since 47% of CF patients have 2 copies of F508del,¹ about half of those with CF in the United States are now eligible for small-molecule therapy. Lumacaftor acts by facilitating transport of a misfolded CFTR to the cell membrane where ivacaftor then increases the probability of an open chloride channel. This combination medication has improved lung function by about 5%.

The ivacaftor/lumacaftor combination was approved by the FDA in July 2015. Both ivacaftor and the ivacaftor/lumacaftor combination were deemed by the FDA to demonstrate statistically significant and sustained FEV₁ improvements over placebo.

The CFF was instrumental in providing financial support for the development of both ivacaftor and the ivacaftor/lumacaftor combination and continues to provide significant research advancement. According to the CFF (www.cff.org), medications currently in the development pipeline include compounds that provide CFTR modulation, surface airway liquid restoration, anti-inflammation, inhaled anti-infection, and pancreatic enzyme function. For more on CFF, see "The traditional CF care model.”^4,20

CORRESPONDENCE
Douglas Lewis, MD, 1121 S. Clifton, Wichita, KS 67218; [email protected].

Influenza-like illness (ILI) activity reached a new national high for the 2015-2016 flu season during the week ending Feb. 20, according to the Centers for Disease Control and Prevention.

Nationwide, the proportion of outpatient visits for ILI was 3.2%, up from 3.1% the week before and well over the national baseline of 2.1%. Arizona and Puerto Rico were still at level 10 on the CDC’s 1-10 scale for ILI activity, and they were joined in the “high” range of activity by California, New Mexico, North Carolina, Texas, and Utah, which were all at level 8, the CDC reported Feb. 26.

States in the “moderate” range of activity for week 19 of the 2015-2016 flu season (week 7 of calendar year 2016) were Arkansas, Florida, and New Jersey at level 7 and Connecticut, Illinois, and Oregon at level 6. There were 13 states in the “low” range of activity – five at level 5 and eight states at level 4 – and 24 states in the “minimal” range, of which 13 were at level 1. Colorado and the District of Columbia had insufficient data to determine activity level, according to data from the CDC’s Outpatient Influenza-like Illness Surveillance Network.

For the week, one flu-related pediatric death, associated with an influenza B virus, was reported to the CDC, bringing the total to 14 for the season. The only states reporting more that one death are California (two) and Florida (three), the CDC said. The average number of deaths for the three previous flu seasons is over 143.

During week 19, a total of 18,844 respiratory specimens were tested, 13.8% of which were positive: 76.1% for influenza A and 23.9% for influenza B. Since Oct. 1, 2015, 4.2% of specimens have tested positive for influenza, with a 70% to 30% split between influenza A and B, the CDC report showed.

[email protected]

Influenza-like illness (ILI) activity reached a new national high for the 2015-2016 flu season during the week ending Feb. 20, according to the Centers for Disease Control and Prevention.

Nationwide, the proportion of outpatient visits for ILI was 3.2%, up from 3.1% the week before and well over the national baseline of 2.1%. Arizona and Puerto Rico were still at level 10 on the CDC’s 1-10 scale for ILI activity, and they were joined in the “high” range of activity by California, New Mexico, North Carolina, Texas, and Utah, which were all at level 8, the CDC reported Feb. 26.

States in the “moderate” range of activity for week 19 of the 2015-2016 flu season (week 7 of calendar year 2016) were Arkansas, Florida, and New Jersey at level 7 and Connecticut, Illinois, and Oregon at level 6. There were 13 states in the “low” range of activity – five at level 5 and eight states at level 4 – and 24 states in the “minimal” range, of which 13 were at level 1. Colorado and the District of Columbia had insufficient data to determine activity level, according to data from the CDC’s Outpatient Influenza-like Illness Surveillance Network.

For the week, one flu-related pediatric death, associated with an influenza B virus, was reported to the CDC, bringing the total to 14 for the season. The only states reporting more that one death are California (two) and Florida (three), the CDC said. The average number of deaths for the three previous flu seasons is over 143.

During week 19, a total of 18,844 respiratory specimens were tested, 13.8% of which were positive: 76.1% for influenza A and 23.9% for influenza B. Since Oct. 1, 2015, 4.2% of specimens have tested positive for influenza, with a 70% to 30% split between influenza A and B, the CDC report showed.

[email protected]

Influenza-like illness (ILI) activity reached a new national high for the 2015-2016 flu season during the week ending Feb. 20, according to the Centers for Disease Control and Prevention.

Nationwide, the proportion of outpatient visits for ILI was 3.2%, up from 3.1% the week before and well over the national baseline of 2.1%. Arizona and Puerto Rico were still at level 10 on the CDC’s 1-10 scale for ILI activity, and they were joined in the “high” range of activity by California, New Mexico, North Carolina, Texas, and Utah, which were all at level 8, the CDC reported Feb. 26.

States in the “moderate” range of activity for week 19 of the 2015-2016 flu season (week 7 of calendar year 2016) were Arkansas, Florida, and New Jersey at level 7 and Connecticut, Illinois, and Oregon at level 6. There were 13 states in the “low” range of activity – five at level 5 and eight states at level 4 – and 24 states in the “minimal” range, of which 13 were at level 1. Colorado and the District of Columbia had insufficient data to determine activity level, according to data from the CDC’s Outpatient Influenza-like Illness Surveillance Network.

For the week, one flu-related pediatric death, associated with an influenza B virus, was reported to the CDC, bringing the total to 14 for the season. The only states reporting more that one death are California (two) and Florida (three), the CDC said. The average number of deaths for the three previous flu seasons is over 143.

During week 19, a total of 18,844 respiratory specimens were tested, 13.8% of which were positive: 76.1% for influenza A and 23.9% for influenza B. Since Oct. 1, 2015, 4.2% of specimens have tested positive for influenza, with a 70% to 30% split between influenza A and B, the CDC report showed.

[email protected]

The overall rate of effectiveness for the 2015-2016 season’s influenza vaccine is 59%, according to preliminary data shared at a Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices meeting.

“This means that getting a flu vaccine this season reduced the risk of having to go to the doctor because of flu by nearly 60%,” Dr. Joseph Bresee – who heads the CDC’s Epidemiology and Prevention Branch – stated in a press release. “It’s good news and underscores the importance and the benefit of both annual and ongoing vaccination efforts this season.”

Copyright CDC

These findings are based on data collected by the U.S. Flu Vaccine Effectiveness Network between November 2, 2015, and February 12, 2016. A 59% effectiveness rate would be roughly in line with what previous years’ vaccines have rated when similar strains of influenza have been prevalent, according to the CDC.

Against the H1N1 strain, which was “responsible for most flu illness this season,” the influenza vaccine was 51% effective. Dr. Bresee noted that the CDC has received reports of unvaccinated individuals this season dying or falling seriously ill because of infection from the H1N1 strain.

The vaccine was 76% effective against all influenza B virus strains, and 79% effective against the B/Yamagata virus strains. There are not enough data at this time, however, to determine the vaccine’s effectiveness against B/Victoria or H3N2 strains.

The CDC cautions that, because the current influenza season is still weeks away from being over, the final rate of vaccine effectiveness for 2015-2016 may change once all the data are analyzed. On average, influenza seasons last 13 weeks.

“Flu activity this season started a bit later and has been lower so far than we’ve seen during the previous three seasons, but activity is still on the upswing and expected to continue for several weeks,” Dr. Bresee stated.

[email protected]

The overall rate of effectiveness for the 2015-2016 season’s influenza vaccine is 59%, according to preliminary data shared at a Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices meeting.

“This means that getting a flu vaccine this season reduced the risk of having to go to the doctor because of flu by nearly 60%,” Dr. Joseph Bresee – who heads the CDC’s Epidemiology and Prevention Branch – stated in a press release. “It’s good news and underscores the importance and the benefit of both annual and ongoing vaccination efforts this season.”

Copyright CDC

These findings are based on data collected by the U.S. Flu Vaccine Effectiveness Network between November 2, 2015, and February 12, 2016. A 59% effectiveness rate would be roughly in line with what previous years’ vaccines have rated when similar strains of influenza have been prevalent, according to the CDC.

Against the H1N1 strain, which was “responsible for most flu illness this season,” the influenza vaccine was 51% effective. Dr. Bresee noted that the CDC has received reports of unvaccinated individuals this season dying or falling seriously ill because of infection from the H1N1 strain.

The vaccine was 76% effective against all influenza B virus strains, and 79% effective against the B/Yamagata virus strains. There are not enough data at this time, however, to determine the vaccine’s effectiveness against B/Victoria or H3N2 strains.

The CDC cautions that, because the current influenza season is still weeks away from being over, the final rate of vaccine effectiveness for 2015-2016 may change once all the data are analyzed. On average, influenza seasons last 13 weeks.

“Flu activity this season started a bit later and has been lower so far than we’ve seen during the previous three seasons, but activity is still on the upswing and expected to continue for several weeks,” Dr. Bresee stated.

[email protected]

The overall rate of effectiveness for the 2015-2016 season’s influenza vaccine is 59%, according to preliminary data shared at a Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices meeting.

“This means that getting a flu vaccine this season reduced the risk of having to go to the doctor because of flu by nearly 60%,” Dr. Joseph Bresee – who heads the CDC’s Epidemiology and Prevention Branch – stated in a press release. “It’s good news and underscores the importance and the benefit of both annual and ongoing vaccination efforts this season.”

Copyright CDC

These findings are based on data collected by the U.S. Flu Vaccine Effectiveness Network between November 2, 2015, and February 12, 2016. A 59% effectiveness rate would be roughly in line with what previous years’ vaccines have rated when similar strains of influenza have been prevalent, according to the CDC.

Against the H1N1 strain, which was “responsible for most flu illness this season,” the influenza vaccine was 51% effective. Dr. Bresee noted that the CDC has received reports of unvaccinated individuals this season dying or falling seriously ill because of infection from the H1N1 strain.

The vaccine was 76% effective against all influenza B virus strains, and 79% effective against the B/Yamagata virus strains. There are not enough data at this time, however, to determine the vaccine’s effectiveness against B/Victoria or H3N2 strains.

The CDC cautions that, because the current influenza season is still weeks away from being over, the final rate of vaccine effectiveness for 2015-2016 may change once all the data are analyzed. On average, influenza seasons last 13 weeks.

“Flu activity this season started a bit later and has been lower so far than we’ve seen during the previous three seasons, but activity is still on the upswing and expected to continue for several weeks,” Dr. Bresee stated.

[email protected]