Functional respiratory imaging identifies redistribution of pulmonary blood flow in patients with COVID-19.

An increasing observation is that some patients with COVID-19 have normal lung compliance but significant hypoxaemia different from typical acute respiratory distress syndrome (ARDS). We hypothesised that changes in pulmonary blood distribution may be partially responsible and used functional respiratory imaging on CT scans to calculate pulmonary blood volume. We found that patients with COVID-19 had significantly reduced blood volume in the smaller calibre blood vessels (here defined as <5 mm2 cross-sectional area) compared with matched ARDS patients and healthy controls. This suggests that using high levels of PEEP may not alone be enough to oxygenate these patients and that additional management strategies may be needed

Interstitial lung disease and specialist palliative care access: a healthcare professionals survey

Background Fibrotic interstitial lung disease is an incurable disease with poor prognosis. We aimed to understand factors affecting decisions regarding referrals to specialist palliative care services and to address barriers and facilitators to referrals from healthcare professionals’ perspectives. Methods A survey study of healthcare professionals, including respiratory physicians, interstitial lung disease nurse specialists, respiratory nurse specialists and palliative care physicians, was conducted using a questionnaire, entailing 17 questions. Results Thirty-six respondents, including 15 interstitial lung disease nurse specialists completed the questionnaire. Symptom control, psychological/spiritual support, general deterioration and end-of-life care were the most common reasons for referrals to specialist palliative care services. Most respondents felt confident in addressing palliative care needs and discussing palliative care with patients. A few participants emphasised that experienced respiratory nurse specialists are well placed to provide symptom management and to ensure continuity of patient care. Participants reported that access to palliative care could be improved by increasing collaborative work between respiratory and palliative care teams. Conclusions Most respondents felt that enhancing access to specialist palliative care services would benefit patients. However, palliative care and respiratory care should not be considered as mutually exclusive and multidisciplinary approach is recommended

CASPA (CArdiac Sarcoidosis in PApworth) improving the diagnosis of cardiac involvement in patients with pulmonary sarcoidosis: protocol for a prospective observational cohort study.

INTRODUCTION: Sarcoidosis is a multisystem disease, predominantly affecting the lungs but can involve the heart, resulting in cardiac sarcoidosis (CS). Patients require MRI/Positron Emission Tomography (PET) scans for diagnosis. Echocardiography, ECG and Holter monitoring may be indicative but not diagnostic alone. Patients can present late with conduction defects, heart failure or sudden death. The CASPA (CArdiac Sarcoidosis in PApworth) study protocol aims to (1) use MRI to identify CS prevalence; (2) use speckle-tracking echocardiography, signal averaged ECG and Holter monitoring to look for diagnostic pathways; and (3) identify serum proteins which may be associated with CS. METHODS AND ANALYSIS: Participants with pulmonary sarcoidosis (and no known cardiac disease) from Royal Papworth Hospital will have the following: cardiac MRI with late gadolinium, two-dimensional transthoracic echocardiography with speckle tracking, signal averaged ECG and 24-hour Holter monitor. They will provide a serum sample for brain natriuretic peptide levels and proteomics by liquid chromatography coupled to high-resolution mass spectrometry. All data will be collected on OpenClinica platform and analysed approximately 6 months after final patient recruitment. ETHICS AND DISSEMINATION: The Camden & Kings Cross Research Ethics Committee approved the protocol (REC number: 17/LO/0667). Integrated Research Approval System (IRAS) 222 720. Dissemination of findings will be via conference presentations and submitted to peer-reviewed journals

Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH):a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial

Background: Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease, with most patients reporting cough. Currently, there are no proven treatments. We examined the use of low dose controlled-release morphine compared with placebo as an antitussive therapy in individuals with idiopathic pulmonary fibrosis. Methods: The PACIFY COUGH study is a phase 2, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial done in three specialist centres in the UK. Eligible patients aged 40–90 years had a diagnosis of idiopathic pulmonary fibrosis within 5 years, self-reported cough (lasting &gt;8 weeks), and a cough visual analogue scale (VAS) score of 30 mm or higher. Patients were randomly assigned (1:1) to placebo twice daily or controlled-release morphine 5 mg orally twice daily for 14 days followed by crossover after a 7-day washout period. Patients were randomised sequentially to a sequence group defining the order in which morphine and placebo were to be given, according to a computer-generated schedule. Patients, investigators, study nurses, and pharmacy personnel were masked to treatment allocation. The primary endpoint was percentage change in objective awake cough frequency (coughs per h) from baseline as assessed by objective digital cough monitoring at day 14 of treatment in the intention-to-treat population, which included all randomised participants. Safety data were summarised for all patients who took at least one study drug and did not withdraw consent. This study was registered at ClinicalTrials.gov, NCT04429516, and has been completed. Findings: Between Dec 17, 2020, and March 21, 2023, 47 participants were assessed for eligibility and 44 were enrolled and randomly allocated to treatment. Mean age was 71 (SD 7·4) years, and 31 (70%) of 44 participants were male and 13 (30%) were female. Lung function was moderately impaired; mean forced vital capacity (FVC) was 2·7 L (SD 0·76), mean predicted FVC was 82% (17·3), and mean predicted diffusion capacity of carbon monoxide was 48% (10·9). Of the 44 patients who were randomised, 43 completed morphine treatment and 41 completed placebo treatment. In the intention-to-treat analysis, morphine reduced objective awake cough frequency by 39·4% (95% CI –54·4 to –19·4; p=0·0005) compared with placebo. Mean daytime cough frequency reduced from 21·6 (SE 1·2) coughs per h at baseline to 12·8 (1·2) coughs per h with morphine, whereas cough rates did not change with placebo (21·5 [SE 1·2] coughs per h to 20·6 [1·2] coughs per h). Overall treatment adherence was 98% in the morphine group and 98% in the placebo group. Adverse events were observed in 17 (40%) of 43 participants in the morphine group and six (14%) of 42 patients in the placebo group. The main side-effects of morphine were nausea (six [14%] of 43 participants) and constipation (nine [21%] of 43). One serious adverse event (death) occurred in the placebo group. Interpretation: In patients with cough related to idiopathic pulmonary fibrosis, low dose controlled-release morphine significantly reduced objective cough counts over 14 days compared with placebo. Morphine shows promise as an effective treatment to palliate cough in patients with idiopathic pulmonary fibrosis, and longer term studies should be the focus of future research. Funding: The Jon Moulton Charity Trust.</p

Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH):a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial

Background: Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease, with most patients reporting cough. Currently, there are no proven treatments. We examined the use of low dose controlled-release morphine compared with placebo as an antitussive therapy in individuals with idiopathic pulmonary fibrosis. Methods: The PACIFY COUGH study is a phase 2, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial done in three specialist centres in the UK. Eligible patients aged 40–90 years had a diagnosis of idiopathic pulmonary fibrosis within 5 years, self-reported cough (lasting &gt;8 weeks), and a cough visual analogue scale (VAS) score of 30 mm or higher. Patients were randomly assigned (1:1) to placebo twice daily or controlled-release morphine 5 mg orally twice daily for 14 days followed by crossover after a 7-day washout period. Patients were randomised sequentially to a sequence group defining the order in which morphine and placebo were to be given, according to a computer-generated schedule. Patients, investigators, study nurses, and pharmacy personnel were masked to treatment allocation. The primary endpoint was percentage change in objective awake cough frequency (coughs per h) from baseline as assessed by objective digital cough monitoring at day 14 of treatment in the intention-to-treat population, which included all randomised participants. Safety data were summarised for all patients who took at least one study drug and did not withdraw consent. This study was registered at ClinicalTrials.gov, NCT04429516, and has been completed. Findings: Between Dec 17, 2020, and March 21, 2023, 47 participants were assessed for eligibility and 44 were enrolled and randomly allocated to treatment. Mean age was 71 (SD 7·4) years, and 31 (70%) of 44 participants were male and 13 (30%) were female. Lung function was moderately impaired; mean forced vital capacity (FVC) was 2·7 L (SD 0·76), mean predicted FVC was 82% (17·3), and mean predicted diffusion capacity of carbon monoxide was 48% (10·9). Of the 44 patients who were randomised, 43 completed morphine treatment and 41 completed placebo treatment. In the intention-to-treat analysis, morphine reduced objective awake cough frequency by 39·4% (95% CI –54·4 to –19·4; p=0·0005) compared with placebo. Mean daytime cough frequency reduced from 21·6 (SE 1·2) coughs per h at baseline to 12·8 (1·2) coughs per h with morphine, whereas cough rates did not change with placebo (21·5 [SE 1·2] coughs per h to 20·6 [1·2] coughs per h). Overall treatment adherence was 98% in the morphine group and 98% in the placebo group. Adverse events were observed in 17 (40%) of 43 participants in the morphine group and six (14%) of 42 patients in the placebo group. The main side-effects of morphine were nausea (six [14%] of 43 participants) and constipation (nine [21%] of 43). One serious adverse event (death) occurred in the placebo group. Interpretation: In patients with cough related to idiopathic pulmonary fibrosis, low dose controlled-release morphine significantly reduced objective cough counts over 14 days compared with placebo. Morphine shows promise as an effective treatment to palliate cough in patients with idiopathic pulmonary fibrosis, and longer term studies should be the focus of future research. Funding: The Jon Moulton Charity Trust.</p

Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH): a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial

Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease, with most patients reporting cough. Currently, there are no proven treatments. We examined the use of low dose controlled-release morphine compared with placebo as an antitussive therapy in individuals with idiopathic pulmonary fibrosis. The PACIFY COUGH study is a phase 2, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial done in three specialist centres in the UK. Eligible patients aged 40-90 years had a diagnosis of idiopathic pulmonary fibrosis within 5 years, self-reported cough (lasting &gt;8 weeks), and a cough visual analogue scale (VAS) score of 30 mm or higher. Patients were randomly assigned (1:1) to placebo twice daily or controlled-release morphine 5 mg orally twice daily for 14 days followed by crossover after a 7-day washout period. Patients were randomised sequentially to a sequence group defining the order in which morphine and placebo were to be given, according to a computer-generated schedule. Patients, investigators, study nurses, and pharmacy personnel were masked to treatment allocation. The primary endpoint was percentage change in objective awake cough frequency (coughs per h) from baseline as assessed by objective digital cough monitoring at day 14 of treatment in the intention-to-treat population, which included all randomised participants. Safety data were summarised for all patients who took at least one study drug and did not withdraw consent. This study was registered at ClinicalTrials.gov, NCT04429516, and has been completed. Between Dec 17, 2020, and March 21, 2023, 47 participants were assessed for eligibility and 44 were enrolled and randomly allocated to treatment. Mean age was 71 (SD 7·4) years, and 31 (70%) of 44 participants were male and 13 (30%) were female. Lung function was moderately impaired; mean forced vital capacity (FVC) was 2·7 L (SD 0·76), mean predicted FVC was 82% (17·3), and mean predicted diffusion capacity of carbon monoxide was 48% (10·9). Of the 44 patients who were randomised, 43 completed morphine treatment and 41 completed placebo treatment. In the intention-to-treat analysis, morphine reduced objective awake cough frequency by 39·4% (95% CI -54·4 to -19·4; p=0·0005) compared with placebo. Mean daytime cough frequency reduced from 21·6 (SE 1·2) coughs per h at baseline to 12·8 (1·2) coughs per h with morphine, whereas cough rates did not change with placebo (21·5 [SE 1·2] coughs per h to 20·6 [1·2] coughs per h). Overall treatment adherence was 98% in the morphine group and 98% in the placebo group. Adverse events were observed in 17 (40%) of 43 participants in the morphine group and six (14%) of 42 patients in the placebo group. The main side-effects of morphine were nausea (six [14%] of 43 participants) and constipation (nine [21%] of 43). One serious adverse event (death) occurred in the placebo group. In patients with cough related to idiopathic pulmonary fibrosis, low dose controlled-release morphine significantly reduced objective cough counts over 14 days compared with placebo. Morphine shows promise as an effective treatment to palliate cough in patients with idiopathic pulmonary fibrosis, and longer term studies should be the focus of future research. The Jon Moulton Charity Trust. [Abstract copyright: Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Nintedanib for non-IPF progressive pulmonary fibrosis: 12-month outcome data from a real-world multicentre observational study

Background Nintedanib slows lung function decline for patients with non-idiopathic pulmonary fibrosis progressive pulmonary fibrosis (PPF) in clinical trials, but the real-world safety and efficacy are not known. Methods In this retrospective cohort study, standardised data were collected from patients in whom nintedanib was initiated for PPF between 2019 and 2020 through an early-access programme across eight centres in the United Kingdom. Rate of lung function change in the 12 months pre- and post-nintedanib initiation was the primary analysis. Symptoms, drug safety, tolerability and stratification by interstitial lung disease subtype and computed tomography pattern were secondary analyses. Results 126 patients were included; 67 (53%) females; mean±sd age 60±13 years. At initiation of nintedanib, mean forced vital capacity (FVC) was 1.87 L (58% predicted) and diffusing capacity of the lung for carbon monoxide (DLCO) was 32.7% predicted. 68% of patients were prescribed prednisolone (median dose 10 mg) and 69% were prescribed a steroid-sparing agent. In the 12 months after nintedanib initiation, lung function decline was significantly lower than in the preceding 12 months: FVC −88.8 mL versus −239.9 mL (p=0.004), and absolute decline in DLCO −2.1% versus −6.1% (p=0.004). Response to nintedanib was consistent in sensitivity and secondary analyses. 89 (71%) out of 126 patients reported side-effects, but 86 (80%) of the surviving 108 patients were still taking nintedanib at 12 months with patients reporting a reduced perception of symptom decline. There were no serious adverse events. Conclusion In PPF, the real-world efficacy of nintedanib replicated that of clinical trials, significantly attenuating lung function decline. Despite the severity of disease, nintedanib was safe and well tolerated in this real-world multicentre study

Outcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease. An International Multicenter Study.

Rationale: The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established.Objectives: To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population.Methods: An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non-idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death.Measurements and Main Results: Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio [HR], 1.60; confidence interval, 1.17-2.18; P = 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR, 1.72; 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39-3.71).Conclusions: Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD