Central processes and cough in idiopathic pulmonary fibrosis

Background: Cough in Idiopathic Pulmonary Fibrosis (IPF) is a debilitating symptom that adversely affects quality of life. Three studies have been performed to advance our understanding of the central processes involved in cough and IPF and lay a foundation for future research. Methods: A multimodal fMRI study was conducted to determine brain structure and cerebrovascular physiology in 17 patients with IPF and 16 matched controls. A cross-sectional questionnaire study was conducted in 120 patients with IPF to determine relationships between psycho-morbidity and cough, measured in 3 different ways (cough VAS, Cough Quality of Life Questionnaire and 24-hour objective cough counts). Multiple regression was used to identify predictors of cough. A subgroup of 12 patients and 11 carers participated in a qualitative interview study to identify cough triggers and relievers, characterise how patients with IPF and their families perceive cough and evaluate its impact on their daily lives. Results: IPF patients have a trend towards reduced grey matter and have reduced cerebral perfusion in areas linked to the default mode network. From interviews, cough is interwoven with breathlessness and fatigue in a spiralling triad. This was supported by the multiple regression analysis that found breathlessness was a significant predictor of all subjective and objective cough measures. Catastrophising is a novel finding which was the only psychological factor to correlate with all three measures of cough. Conclusions: Patients with IPF can tolerate brain fMRI, and the results support further investigation of central cough mechanisms, such as cough challenge testing, in this population. Additional physiological information should be simultaneously collected to advance understanding of abnormal cerebral physiology and its impact. The neural relationship between breathlessness, cough, and catastrophising should be evaluated as there may be a shared common pathway that is amenable to treatment

Mycophenolate and azathioprine efficacy in interstitial lung disease: a systematic review and meta-analysis

Objectives Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD.Design Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only.Eligibility criteria Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded.Data synthesis The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I2 evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design.Results A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI −4.00 to 9.88, I2=79.3%; %DLco −2.03, 95% CI −4.38 to 0.32, I2=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I2=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DLCO (95% CI 2.05 to 6.79, I2=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence.Conclusions There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD.PROSPERO registration number CRD42023423223