Severe chronic cough relating to post-COVID-19 interstitial lung disease: a case report.

Cough is a common symptom occurring in patients with acute coronavirus disease 2019 (COVID-19) infection as well as during the post-COVID-19 period. The post-COVID-19 cough can improve over time and the incidence of sustained post-COVID-19 chronic cough is low. Approaching post-COVID-19 cough is challenging to clinicians including pulmonologists and allergists due to a diverse set of etiologies and the lack of published guidance on effective treatments. A 60-year-old male ex-smoker presented to the outpatient long COVID-19 clinic because of a prolonged cough for 4 months after a severe COVID-19 infection. His cough was so violent that he had suffered a spontaneous pneumothorax on 2 occasions. In addition, he also complained of exertional breathlessness. Due to concerns over ongoing systemic inflammation from COVID-19 or thromboembolism, a serum C-reactive protein and d-dimer where checked and were normal. Chest computed tomography (CT) images revealed diffuse ground glass opacities combined with scattered emphysema in the bilateral upper lobes and several small bullae located close to the pleura. His diagnosis was post-COVID-19 interstitial lung disease (ILD) and he was treated with methylprednisolone 32 mg/day. After 2 weeks of treatment, he showed improvement with near cessation of cough and a significant decline in dyspnea. The follow-up chest CT also showed improvement in the ground glass opacities. Severe chronic cough could be a manifestation of post-COVID-19 ILD. This case demonstrates the use of systemic corticosteroid to improve both post-COVID-19 ILD and its associated chronic cough.

Pirfenidone in fibrotic hypersensitivity pneumonitis: a double-blind, randomised clinical trial of efficacy and safety.

BACKGROUND: Fibrotic hypersensitivity pneumonitis (FHP) is an irreversible lung disease with high morbidity and mortality. We sought to evaluate the safety and effect of pirfenidone on disease progression in such patients. METHODS: We conducted a single-centre, randomised, double-blinded, placebo-controlled trial in adults with FHP and disease progression. Patients were assigned in a 2:1 ratio to receive either oral pirfenidone (2403 mg/day) or placebo for 52 weeks. The primary end point was the mean absolute change in the per cent predicted forced vital capacity (FVC%). Secondary end points included progression-free survival (PFS, time to a relative decline ≥10% in FVC and/or diffusing capacity of the lung for carbon monoxide (DLCO), acute respiratory exacerbation, a decrease of ≥50 m in the 6 min walk distance, increase or introduction of immunosuppressive drugs or death), change in FVC slope and mean DLCO%, hospitalisations, radiological progression of lung fibrosis and safety. RESULTS: After randomising 40 patients, enrolment was interrupted by the COVID-19 pandemic. There was no significant between-group difference in FVC% at week 52 (mean difference -0.76%, 95% CI -6.34 to 4.82). Pirfenidone resulted in a lower rate of decline in the adjusted FVC% at week 26 and improved PFS (HR 0.26, 95% CI 0.12 to 0.60). Results for other secondary end points showed no significant difference between groups. No deaths occurred in the pirfenidone group and one death (respiratory) occurred in the placebo group. There were no treatment-emergent serious adverse events. CONCLUSIONS: The trial was underpowered to detect a difference in the primary end point. Pirfenidone was found to be safe and improved PFS in patients with FHP. TRIAL REGISTRATION MUMBER: NCT02958917.

Safety, tolerability, and efficacy of pirfenidone in patients with rheumatoid arthritis-associated interstitial lung disease: a randomised, double-blind, placebo-controlled, phase 2 study.

BACKGROUND: Interstitial lung disease is a known complication of rheumatoid arthritis, with a lifetime risk of developing the disease in any individual of 7·7%. We aimed to assess the safety, tolerability, and efficacy of pirfenidone for the treatment of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: TRAIL1 was a randomised, double-blind, placebo-controlled, phase 2 trial done in 34 academic centres specialising in interstitial lung disease in four countries (the UK, the USA, Australia, and Canada). Adults aged 18-85 years were eligible for inclusion if they met the 2010 American College of Rheumatology and European Alliance of Associations for Rheumatology criteria for rheumatoid arthritis and had interstitial lung disease on a high-resolution CT scan imaging and, when available, lung biopsy. Exclusion criteria include smoking, clinical history of other known causes of interstitial lung disease, and coexistant clinically significant COPD or asthma. Patients were randomly assigned (1:1) to receive 2403 mg oral pirfenidone (pirfenidone group) or placebo (placebo group) daily. The primary endpoint was the incidence of the composite endpoint of a decline from baseline in percent predicted forced vital capacity (FVC%) of 10% or more or death during the 52-week treatment period assessed in the intention-to-treat population. Key secondary endpoints included change in absolute and FVC% over 52 weeks, the proportion of patients with a decline in FVC% of 10% or more, and the frequency of progression as defined by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02808871. FINDINGS: From May 15, 2017, to March 31, 2020, 231 patients were assessed for inclusion, of whom 123 patients were randomly assigned (63 [51%] to the pirfenidone group and 60 [49%] to the placebo group). The trial was stopped early (March 31, 2020) due to slow recruitment and the COVID-19 pandemic. The difference in the proportion of patients who met the composite primary endpoint (decline in FVC% from baseline of 10% or more or death) between the two groups was not significant (seven [11%] of 63 patients in the pirfenidone group vs nine [15%] of 60 patients in the placebo group; OR 0·67 [95% CI 0·22 to 2·03]; p=0·48). Compared with the placebo group, patients in the pirfenidone group had a slower rate of decline in lung function, measured by estimated annual change in absolute FVC (-66 vs -146; p=0·0082) and FVC% (-1·02 vs -3·21; p=0·0028). The groups were similar with regards to the decline in FVC% by 10% or more (five [8%] participants in the pirfenidone group vs seven [12%] in the placebo group; OR 0·52 [95% CI 0·14-1·90]; p=0·32) and the frequency of progression as defined by OMERACT (16 [25%] in the pirfenidone group vs 19 [32%] in the placebo group; OR 0·68 [0·30-1·54]; p=0·35). There was no significant difference in the rate of treatment-emergent serious adverse events between the two groups, and there were no treatment-related deaths. INTERPRETATION: Due to early termination of the study and underpowering, the results should be interpreted with caution. Despite not meeting the composite primary endpoint, pirfenidone slowed the rate of decline of FVC over time in patients with RA-ILD. Safety in patients with RA-ILD was similar to that seen in other pirfenidone trials. FUNDING: Genentech.

Severe chronic cough relating to post-COVID-19 interstitial lung disease: a case report

Cough is a common symptom occurring in patients with acute coronavirus disease 2019 (COVID-19) infection as well as during the post-COVID-19 period. The post-COVID-19 cough can improve over time and the incidence of sustained post-COVID-19 chronic cough is low. Approaching post-COVID-19 cough is challenging to clinicians including pulmonologists and allergists due to a diverse set of etiologies and the lack of published guidance on effective treatments. A 60-year-old male ex-smoker presented to the outpatient long COVID-19 clinic because of a prolonged cough for 4 months after a severe COVID-19 infection. His cough was so violent that he had suffered a spontaneous pneumothorax on 2 occasions. In addition, he also complained of exertional breathlessness. Due to concerns over ongoing systemic inflammation from COVID-19 or thromboembolism, a serum C-reactive protein and d-dimer where checked and were normal. Chest computed tomography (CT) images revealed diffuse ground glass opacities combined with scattered emphysema in the bilateral upper lobes and several small bullae located close to the pleura. His diagnosis was post-COVID-19 interstitial lung disease (ILD) and he was treated with methylprednisolone 32 mg/day. After 2 weeks of treatment, he showed improvement with near cessation of cough and a significant decline in dyspnea. The follow-up chest CT also showed improvement in the ground glass opacities. Severe chronic cough could be a manifestation of post-COVID-19 ILD. This case demonstrates the use of systemic corticosteroid to improve both post-COVID-19 ILD and its associated chronic cough.

CT of Post-Acute Lung Complications of COVID-19.

The acute course of COVID-19 is variable and ranges from asymptomatic infection to fulminant respiratory failure. Patients recovering from COVID-19 can have persistent symptoms and CT abnormalities of variable severity. At 3 months after acute infection, a subset of patients will have CT abnormalities that include ground-glass opacity (GGO) and subpleural bands with concomitant pulmonary function abnormalities. At 6 months after acute infection, some patients have persistent CT changes to include the resolution of GGOs seen in the early recovery phase and the persistence or development of changes suggestive of fibrosis, such as reticulation with or without parenchymal distortion. The etiology of lung disease after COVID-19 may be a sequela of prolonged mechanical ventilation, COVID-19-induced acute respiratory distress syndrome (ARDS), or direct injury from the virus. Predictors of lung disease after COVID-19 include need for intensive care unit admission, mechanical ventilation, higher inflammatory markers, longer hospital stay, and a diagnosis of ARDS. Treatments of lung disease after COVID-19 are being investigated, including the potential of antifibrotic agents for prevention of lung fibrosis after COVID-19. Future research is needed to determine the long-term persistence of lung disease after COVID-19, its impact on patients, and methods to either prevent or treat it. © RSNA, 2021.