Cough In Idiopathic Pulmonary Fibrosis Research Articles

P9 Cough Is Prevalent In Higher Proportion Of Older Patients With Both Idiopathic Pulmonary Fibrosis And Non-specific Interstitial Lung Disease

Introduction Cough is a major symptom of Idiopathic Pulmonary fibrosis (IPF), a progressive, fatal lung disease with median survival of 3 years. The first study to suggest cough as an independent predictor of disease progression, reported it in 84% of the population. 1 The only study to quantify cough in 19 IPF patients, reported strong correlation between objective cough counts and cough related quality of life 2 There is a lack of studies investigating the prevalence, pathogenesis or treatment of cough in IPF. We set up a study to evaluate the prevalence of cough in an incident IPF and Non specific Interstitial Pneumonia (NSIP) population. Methods A prospective, multi-centre, observational, cohort study, PROFILE-Central England (September 2009 to June 2014) was set up. Patients had a diagnosis of definite or probable IPF or NSIP based on the ATS consensus. Leicester cough questionnaire (LCQ) was used to assess presence or absence of cough at baseline. Furthermore,the cohort was divided into 3 groups to assess severity of cough: Mild (17–20), Moderate (11–16.9) and Severe ( Results 312 incident patients with IPF or NSIP were enrolled. 261/312(83.6%) patients had incident IPF whilst 51/312(16.4%) had NSIP. The mean age of the cohort was 73.5 years (35–90 years). 235/312(76%) were males with mean age 73.7 years (47–90 years); 74/312(24%) were females with mean age of 72.9 years (35.8–88.8 years). 261/312(83.6%) reported cough compared with 51/312(16.4%) who reported no cough. Of the patients who reported cough, 45/261(17.2%) had severe cough, 112/261(42.9%) had moderate cough and 104/261(39.8%) had mild cough. There was no effect of gender, however, older cohort reported more cough (age >55 years; p = 0.014). Smoking may be a confounder, however the number of current smokers in the cohort is too small (p = 0.05). Interestingly both NSIP and IPF cohort reported cough; however, proportionally NSIP patients have less cough (14/51,27.4%) compared with IPF (37/261, 14%). Conclusions Cough occurs in a huge majority of patients with both IPF and NSIP. Cough appears to be a greater problem in older patients. References Ryerson CJ et al . Cough predicts prognosis in idiopathic pulmonary fibrosis. Respirology . 2011 Aug;16(6):969–75 Key AL et al . Objective cough frequency in Idiopathic Pulmonary Fibrosis. Cough . 2010;6:4

Mechanisms and Treatment of Cough in Idiopathic Pulmonary Fibrosis

Mechanisms and Treatment of Cough in Idiopathic Pulmonary Fibrosis

Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study.

BackgroundChronic cough affects more than 70 percent of patients with Idiopathic Pulmonary Fibrosis and causes significant morbidity. Gastroesophageal reflux is the cause of some cases of chronic cough; and also has a postulated role in the aetiology of Idiopathic Pulmonary Fibrosis. A high prevalence of acid; and more recently non-acid, reflux has been observed in Idiopathic Pulmonary Fibrosis cohorts. Therefore, gastroesophageal reflux may be implicated in the pathogenesis of cough in Idiopathic Pulmonary Fibrosis.MethodsEighteen subjects with Idiopathic Pulmonary Fibrosis underwent 24-hour oesophageal impedance and cough count monitoring after the careful exclusion of causes of chronic cough other than gastroesophageal reflux. All 18 were then treated with high dose acid suppression therapies. Fourteen subjects underwent repeat 24-hour oesophageal impedance and cough count monitoring after eight weeks.ResultsTotal reflux and acid reflux frequencies were within the normal range in the majority of this cohort. The frequencies of non-acid and proximal reflux events were above the normal range. Following high dose acid suppression therapy there was a significant decrease in the number of acid reflux events (p = 0.02), but an increase in the number of non-acid reflux events (p = 0.01). There was no change in cough frequency (p = 0.70).ConclusionsThis study confirms that non-acid reflux is prevalent; and that proximal oesophageal reflux occurs in the majority, of subjects with Idiopathic Pulmonary Fibrosis. It is the first study to investigate the effect of acid suppression therapy on gastroesophageal reflux and cough in patients with Idiopathic Pulmonary Fibrosis. The observation that cough frequency does not improve despite verifiable reductions in oesophageal acid exposure challenges the role of acid reflux in Idiopathic Pulmonary Fibrosis associated cough. The finding that non-acid reflux is increased following the use of acid suppression therapies cautions against the widespread use of acid suppression in patients with Idiopathic Pulmonary Fibrosis given the potential role for non-acid reflux in the pathogenesis of cough and Idiopathic Pulmonary Fibrosis itself.Study registrationThe study was registered with the Cardiff and Vale University Local Health Board Research and Development Committee (09/CMC/4619) and the South East Wales Ethics Committee (09/WSE04/57).

Severity of cough in idiopathic pulmonary fibrosis is associated with MUC5 B genotype

BackgroundA polymorphism (rs35705950) in the promoter region of the mucin MUC5B is associated with both familial and sporadic forms of idiopathic pulmonary fibrosis. (IPF) We hypothesize that this common MUC5B variant will impact the expression of cough, a frequent disabling symptom seen in subjects with IPF.MethodsWe genotyped 136 subjects with IPF. All living subjects were provided with a Leicester Cough Questionnaire (LCQ) to measure cough severity. We assessed allele effects of the MUC5B polymorphism on the LCQ scores using SAS General Linear Models (GLM) in the patients with IPF.ResultsIn the 68 of the total 136 IPF patients who returned the LCQ, MUC5B minor allele frequency (T) is consistent with prior published studies (31%). We found a significant independent effect of the T allele on the LCQ score (p = 0.002 for subjects with IPF). This effect is independent of other common causes of cough, including gastroesophogeal reflux disease and upper airway cough syndrome.ConclusionsCough severity, a common disabling phenotypic component of IPF, is significantly associated with the presence of the minor allele of a MUC5B promoter polymorphism. This study highlights a possible genetic mechanism for phenotypic heterogeneity in pulmonary fibrosis.

Validation of the Cough Quality-of-Life Questionnaire in Patients With Idiopathic Pulmonary Fibrosis

Cough is a pervasive and disabling symptom of idiopathic pulmonary fibrosis (IPF) and is an independent predictor of disease progression. The Cough Quality-of-Life Questionnaire (CQLQ) is a validated measure of cough-specific quality of life that could be used as an outcome measure in therapeutic trials for IPF. This study aimed to assess the reliability and validity of the CQLQ in individuals with IPF. The CQLQ was administered as an outcome within a previously published 27-week, placebo-controlled, crossover trial of thalidomide for cough in IPF. Participants were adults with IPF and chronic cough. A cough visual analog scale (VAS) and the St. George's Respiratory Questionnaire (SGRQ) were administered to establish concurrent validity of the CQLQ. Internal consistency was high (Cronbach α > .70) for the CQLQ total and four of six subscale scores. The CQLQ total score demonstrated concurrent validity through significant correlations with scores on the cough VAS and SGRQ total and subscale scores (r range, 0.63-0.81; P < .05). The intraclass correlation coefficient for the CQLQ completed at baseline and after a therapeutic washout period at week 15 was 0.87, indicating very good test-retest reliability. This study supports the use of the CQLQ as a valid and reliable instrument in IPF and should be used to assess cough-specific quality of life in therapeutic trials.

Thalidomide for the Treatment of Cough in Idiopathic Pulmonary Fibrosis

Letters19 March 2013Thalidomide for the Treatment of Cough in Idiopathic Pulmonary FibrosisNoah Lechtzin, MD, MHS and Maureen R. Horton, MDNoah Lechtzin, MD, MHSFrom Johns Hopkins University School of Medicine, Baltimore, Maryland.Search for more papers by this author and Maureen R. Horton, MDFrom Johns Hopkins University School of Medicine, Baltimore, Maryland.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-158-6-201303190-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We appreciate Dr. Swigris and colleagues' interest in our article and would like to respond to their questions regarding the CQLQ (1), the VAS of cough, and the SGRQ (2).The CQLQ is a 28-item instrument developed and validated in a cohort of patients with idiopathic cough and as such contains some questions that are not relevant to patients with IPF. However, the CQLQ contains many questions that are applicable to virtually anyone with a severe cough. There are 6 subscales of the CQLQ: physical complaints, psychosocial issues, functional abilities, emotional well-being, extreme physical complaints, and personal safety ...

Thalidomide for the Treatment of Cough in Idiopathic Pulmonary Fibrosis

Thalidomide for the Treatment of Cough in Idiopathic Pulmonary Fibrosis

Thalidomide for the Treatment of Cough in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder of unknown cause with no effective treatment. Cough affects up to 80% of patients with IPF, is frequently disabling, and lacks effective therapy. To determine the efficacy of thalidomide in suppressing cough in patients with IPF. 24-week, double-blind, 2-treatment, 2-period crossover trial. (ClinicalTrials.gov registration number: NCT00600028) 1 university center. 98 participants were screened, 24 were randomly assigned, 23 received treatment (78.3% men; mean age, 67.6 years; mean FVC, 70.4% predicted), and 20 completed both treatment periods. The primary end point was cough-specific quality of life measured by the Cough Quality of Life Questionnaire (CQLQ). Secondary end points were visual analogue scale of cough and the St. George's Respiratory Questionnaire (SGRQ). For all measures, lower scores equaled improved cough or respiratory quality of life. CQLQ scores significantly improved with thalidomide (mean difference vs. placebo, -11.4 [95% CI, -15.7 to -7.0]; P < 0.001). Thalidomide also significantly improved scores on the visual analogue scale of cough (mean difference vs. placebo, -31.2 [CI, -45.2 to -17.2]; P < 0.001). In participants receiving thalidomide, scores from the total SGRQ, SGRQ symptom domain, and SGRQ impact domain improved compared with those of participants receiving placebo. Adverse events were reported in 74% of patients receiving thalidomide and 22% receiving placebo; constipation, dizziness, and malaise were more frequent with thalidomide. This was a single-center study of short duration and small sample size focused on symptom-specific quality of life. Thalidomide improved cough and respiratory quality of life in patients with IPF. A larger trial is warranted to assess these promising results. Celgene Corporation.

Mechanical induction of cough in Idiopathic Pulmonary Fibrosis

BackgroundPatients with idiopathic pulmonary fibrosis (IPF) frequently develop a dry, irritating cough which often proves refractory to anti-tussive therapies. The precise pathogenetic mechanisms responsible for this cough are unknown. We hypothesised that changes in nerves modulating mechanical sensitivity in areas of interstitial fibrosis might lead to enhanced cough response to mechanical stimulation of the chest in IPF.MethodsWe studied 27 non-smoking subjects with IPF (63% male), mean (SD) age 71.7 (7) years and 30 healthy non-smokers. Quality of life (Leicester Cough Questionnaire), cough symptom scores and cough severity scores (visual analog scales) were recorded. Percussion stimulation was applied over the posterior lung base, upper anterior chest and manubrium sternum at sequential frequencies (20 Hertz (Hz), 40 Hz and 60 Hz) for up to 60 seconds and repeated twice at two minute intervals. The number of subjects achieving two and five-cough responses, total cough counts and cough latency were recorded. In separate experiments, the effect of mechanical stimulation on the pattern of breathing was determined in eight IPF subjects and five control subjects.ResultsIn patients with IPF, we demonstrated strong correlations between subjective cough measurements, particularly the cough symptom score and Leicester Cough Questionnaire (r = -0.86; p < 0.001). Mechanical percussion induced a true cough reflex in 23/27 (85%) IPF subjects, but only 5/30 (17%) controls (p < 0.001). More patients with IPF reached the two-cough response at a lower frequency (20 Hz) posteriorly than at other positions. Highest mean cough totals were seen with stimulation at or above 40 Hz. Mechanical stimulation had no effect on respiratory rate but increased tidal volume in four (50%) subjects with IPF, particularly at higher frequencies. It was associated with increased urge to cough followed by a true cough reflex.ConclusionsThis study demonstrates that patients with IPF show enhanced cough reflex sensitivity to mechanical stimulation of the chest wall whilst normal individuals show little or no response. The observation that low frequency stimulation over the lung base, where fibrosis is most extensive, induces cough in more patients than at other sites supports the hypothesis that lung distortion contributes to the pathogenesis of cough in IPF.

Objective cough frequency in Idiopathic Pulmonary Fibrosis

BackgroundCough is a common presenting symptom in patients with Idiopathic Pulmonary Fibrosis (IPF). This study measured cough rates in IPF patients and investigated the association between cough and measures of health related quality of life and subjective cough assessments. In addition, IPF cough rates were related to measures of physiological disease severity and compared to cough rates in health and other respiratory conditions.MethodsNineteen IPF patients, mean age 70.8 years ± 8.6, five female (26.3%) were studied. Subjects performed full pulmonary function testing, 24 hour ambulatory cough recordings, completed a cough related quality of life questionnaire (Leicester Cough Questionnaire) and subjectively scored cough severity with a visual analogue scale. Ambulatory cough recordings were manually counted and reported as number of coughs per hour.ResultsThe 24hr cough rates were high (median 9.4, range 1.5-39.4), with day time rates much higher than night time (median 14.6, range 1.9-56.6 compared to 1.9, range 0-19.2, p = 0.003). Strong correlations were found between objective cough frequency and both the VAS (day r = 0.80, p < 0.001, night r = 0.71, p = 0.001) and LCQ (r = -0.80, p < 0.001), but not with measures of pulmonary function. Cough rates in IPF were higher than healthy subjects (p < 0.001) and asthma patients (p < 0.001) but similar to patients with chronic cough (p = 0.33).ConclusionsThis study confirms objectively that cough is a major, very distressing and disabling symptom in IPF patients. The strong correlations between objective cough counts and cough related quality of life measures suggest that in IPF patient's, perception of cough frequency is very accurate.

A study of the cough reflex in idiopathic pulmonary fibrosis.

Little is known about the pathogenesis of cough in idiopathic pulmonary fibrosis (IPF). We hypothesized that abnormalities of respiratory tract tachykinin-containing sensory nerves may be implicated. We studied cough response to capsaicin, substance P (SP), and bradykinin in 10 healthy control subjects and 10 patients with IPF. Six patients were tested before and after steroid therapy. Induced sputum cell counts and neurotrophic factor levels were also measured in 13 patients and 13 control subjects. The results show that cough sensitivity to capsaicin was greater in patients (p < 0.01). Neither SP nor bradykinin induced cough in normal subjects. SP and bradykinin induced cough in 7/10 patients (p < 0.002) and 2/10 patients (not significant) with IPF, respectively. Prednisolone caused a reduction in cough sensitivity to capsaicin (p < 0.05) and SP (p < 0.05) in all six patients treated. There were significantly more neutrophils (p = 0.001) and higher levels of nerve growth factor (p < 0.01) and brain-derived neurotrophic factor (p < 0.01) in patient's sputa. These findings suggest functional upregulation of lung sensory neurones in IPF. The cough response to inhaled SP in most patients may reflect disrupted respiratory epithelium. The response to corticosteroids demonstrates that the cough is amenable to therapy.