This study is the first to quantify cough in IPF patients and examine the relationships between objective cough rates and subjective measures. The IPF patients had frequent coughing, especially during the day, with relatively little nocturnal cough. Cough rates were wide ranging, did not appear to be influenced by the patient's age or gender and were highly reproducible between investigators and over a short period of time. A comparison between objective cough rates in IPF with other conditions associated with cough, showed that mean cough rates in this group of IPF patients were higher than in asthma but comparable to rates found in patients with an isolated chronic cough presenting to a specialist clinic.
In this study two subjective assessments of cough were employed, the LCQ and a Visual Analogue Scale. The LCQ is a fully validated questionnaire that provides an estimation of the physical, psychological and social impact of cough as well as providing a measure of the overall impact of coughing. In contrast the VAS is a simple measure that estimates the global impact of cough during the day and night. There was a strong and statistically significant relationship with cough rates and both of these measures. The LCQ correlated with both day and to a lesser degree night time coughing for all the domains. In view of the small numbers of coughs this night-time association was not expected. However, it is known that IPF is associated with sleep fragmentation and thus it is likely that any episode of nocturnal coughing will wake these patients .
The VAS performed similarly to the LCQ. The daytime VAS score (mean 33.40 mm, ± 25.33) is comparable to that from previous data in IPF (mean IPF 30 mm ± 19 and 40 mm ± 25 mm [17, 18],). These strong correlations between objective cough counts and cough related quality of life measures suggest that in IPF patients perception of cough frequency is very accurate. These relationships appear to be stronger than those reported by patients presenting specifically with the symptom of chronic cough. Perhaps heightened awareness of coughing occurs in the context of breathlessness, or because coughing from restricted lung volumes requires greater effort. It is interesting that Doherty et al did not find an association between cough VAS and cough reflex sensitivity measured by capsaicin challenge , suggesting that the cough reflex sensitivity in IPF is not a very sensitive predictor of actual cough rates.
Exploring the association between cough frequency and measures of disease severity using pulmonary function showed no correlation between more advanced disease (e.g. lower TLC and DLco) and cough rates. In fact the only weak positive correlation was with total cough rates and higher TLC%. This is likely to be a chance result as the study was not designed nor powered to look for this association. However, the fact that there is no strong correlation between pulmonary function and cough rates suggests that cough is an established and troublesome symptom by the time patients present with this disease. A larger study is required to look at this association but these results suggest that cough may not be a good surrogate for disease progression.
The exact mechanisms underlying cough in IPF remain unclear, in particular why coughing should occur when the cough receptors are proximal whilst the main disease process is in the parenchyma. Several theories have been proposed to explain this observation and the similarity between the cough rates in IPF and chronic cough patients raises the possibility that there may be similar mechanisms at work in these two apparently disparate groups. For example, Irwin suggested that in a group of patients with known ILD referred to a specialist cough clinic, 50% had evidence of asthma, nasal or gastrooesophageal reflux disease (GORD); GORD in particular is thought to be highly prevalent in IPF . However, it is equally possible that IPF directly causes cough as inflammation is not limited to the parenchyma and airway inflammatory mediators known to provoke cough have been detected . In keeping with this suggestion increased levels of albumin in the sputum of IPF patients have been reported which suggests disrupted airway epithelium . Such damage is accompanied by neutrophilic inflammation, raised levels of nerve growth factor and brain derived neurotrophic factor . A further possible cause of cough in these patients is airway distortion secondary to interstitial fibrosis which results in traction bronchiectasis.