Cough Frequency May Evaluate Cystic Fibrosis Treatments
PTC Therapeutics today announced new data suggesting that the quantification of cough frequency may offer a clinically meaningful outcome measure in cystic fibrosis (CF). Cough is one of the most prominent and burdensome disease-related symptoms in CF. According to data presented today at the 2008 International Conference of the American Thoracic Society, patients with CF cough a remarkable 324 to 1,569 times per day, with an average of 643 coughs per day. In comparison, healthy individuals generally cough fewer than 16 times in an entire day, according to the European Respiratory Journal (Hsu 1994).
"Cough is one of the major symptomatic manifestations of the underlying disease process in CF," stated Eitan Kerem, M.D., head of the Department of Pediatrics and Cystic Fibrosis Center, Hadassah University Hospital. "Chronic excessive coughing is a burden on CF patients and a source of anxiety for caregivers and loved ones. Frequent and intense coughing has a profound effect on the overall quality of life of the patient -- compromising work, school, sleep and social interactions."
CF is among the most common life-threatening genetic disorders worldwide and affects nearly 70,000 adults and children. Patients with CF lack the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a chloride ion channel that maintains proper hydration of epithelial cells in the lungs, pancreas, and liver. Loss of the CFTR protein leads to chronic airway inflammation in association with obstruction and mucopurulent secretions, all of which provoke persistent coughing. While there are approved palliative treatments for CF, clinical development efforts would benefit from reliable quantitative endpoints that are clinically meaningful because they directly measure changes in how a patient feels and functions.
"The ability to quantify cough represents a significant step forward in our understanding of one of the most prominent symptoms of CF," added Preston Campbell, III, M.D., Executive Vice President of Medical Affairs at the Cystic Fibrosis Foundation. "A significant reduction in cough frequency would be of real value to patients."
The study was designed to assess cough frequency as a measure of clinical benefit. Quantitative measurement was achieved using a new technology, the VivoMetrics LifeShirt, which integrates cough signals from chest wall motion transducers and a throat microphone and stores the data for computer analysis. FEV1 (Forced Expiratory Volume in the first second) and FVC (forced vital capacity) -- key measures of lung function -- were assessed by spirometry, and patients completed a symptom survey.
Patients included 19 adults not in CF exacerbation. Although there was occasional neck pressure due to the throat microphone, compliance was excellent, with cough data collected for a median of 24 hours. Cough frequency averaged 643 coughs per day (ranging from 324 to 1,569 coughs per day) and tended to increase with lower FEV1 and greater age.
"Anecdotal information concerning cough frequency in CF patients led us to assess cough quantitatively using the LifeShirt," said Langdon Miller, M.D., Chief Medical Officer of PTC. "The cough frequency data announced today highlights the potential for cough assessment as an outcome measure that may be used in the development of new therapies for CF. We look forward to presenting data on the effect of PTC124 on cough frequency at the 31st annual European Cystic Fibrosis Society Conference in June, and to initiating longer-term trials later this year to further evaluate the clinical efficacy of PTC124 in patients with CF."