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.

Metal worker's lung: spatial association with Mycobacterium avium.

BACKGROUND: Outbreaks of hypersensitivity pneumonitis (HP) are not uncommon in workplaces where metal working fluid (MWF) is used to facilitate metal turning. Inhalation of microbe-contaminated MWF has been assumed to be the cause, but previous investigations have failed to establish a spatial relationship between a contaminated source and an outbreak. OBJECTIVES: After an outbreak of five cases of HP in a UK factory, we carried out blinded, molecular-based microbiological investigation of MWF samples in order to identify potential links between specific microbial taxa and machines in the outbreak zone. METHODS: Custom-quantitative PCR assays, microscopy and phylogenetic analyses were performed on blinded MWF samples to quantify microbial burden and identify potential aetiological agents of HP in metal workers. MEASUREMENTS AND MAIN RESULTS: MWF from machines fed by a central sump, but not those with an isolated supply, was contaminated by mycobacteria. The factory sump and a single linked machine at the centre of the outbreak zone, known to be the workstation of the index cases, had very high levels of detectable organisms. Phylogenetic placement of mycobacterial taxonomic marker genes generated from these samples indicated that the contaminating organisms were closely related to Mycobacterium avium. CONCLUSIONS: We describe, for the first time, a close spatial relationship between the abundance of a mycobacterium-like organism, most probably M. avium, and a localised outbreak of MWF-associated HP. The further development of sequence-based analytic techniques should assist in the prevention of this important occupational disease.

Hypersensitivity pneumonitis in workers exposed to metalworking fluids.

BACKGROUND: This study used data from a large UK outbreak investigation, to develop and validate a new case definition for hypersensitivity pneumonitis due to metalworking fluid exposure (MWF-HP). METHODS: The clinical data from all workers with suspected MWF-HP were reviewed by an experienced panel of clinicians. A new MWF-HP Score was then developed to match the "gold standard" clinical opinion as closely as possible, using standard diagnostic criteria that were relatively weighted by their positive predictive value. RESULTS: The new case definition was reproducible, and agreed with expert panel opinion in 30/37 cases. This level of agreement was greater than with any of the three previously utilized case definitions (agreement in 16-24 cases). Where it was possible to calculate, the MWF-HP Score also performed well when applied to 50 unrelated MWF-HP cases. CONCLUSIONS: The MWF-HP Score offers a new case definition for use in future outbreaks.

Systematic review of respiratory outbreaks associated with exposure to water-based metalworking fluids.

INTRODUCTION: Potential demographic risk factors for outbreaks of respiratory disease due to water-based metalworking fluids (MWFs) were investigated through systematic review of published outbreak investigations. METHODS: Search terms were selected by a multidisciplinary team, assisted by an experienced library information service. Several computerized literature databases were searched for articles published between January 1990 and October 2011, relating to ill health outbreaks due to MWFs. Papers meeting the search criteria were reviewed in detail, and their references checked for additional articles. Study design and demographic details of the outbreak were extracted from the selected articles and entered into standardized evidence tables. RESULTS: Thirty-five articles relating to investigations of 27 outbreaks of respiratory ill health attributed to MWF exposure were identified. The majority of reports were case series of disease or observational cross-sectional studies of symptoms and hygiene measurements. Eight of the outbreak investigations included an element of case-control analysis. Most outbreaks were from the USA, had occurred in large car- or aeronautical-manufacturing plants, and were associated with the use of central shared sumps. Hygiene studies have not demonstrated consistent risk factors for respiratory outbreaks, in terms of the type of MWF utilized, degree of microbial contamination, or levels of personal exposure. Six studies were identified that found workers with MWF exposure during outbreaks were more likely to report respiratory or systemic symptoms than unexposed control workers. Six case-control analyses were also identified that found workers with extrinsic allergic alveolitis (EAA) were more likely to demonstrate certain immune responses to microbial contaminants and/or used MWFs than workers without EAA. CONCLUSION: Despite a number of detailed workplace and immunological studies of asthma and alveolitis outbreaks in MWF-exposed workforces, our understanding of their aetiology remains limited.

Barriers to identifying occupational asthma among primary healthcare professionals: a qualitative study.

INTRODUCTION: Occupational asthma (OA) accounts for one in six cases of adult-onset asthma and is associated with a large societal cost. Many cases of OA are missed or delayed, leading to ongoing exposure to the causative agent and avoidable lung function loss and poor employment-related outcomes. Enquiry about work-related symptoms and the nature of work by healthcare professionals (HCPs) is limited, evident in primary and secondary care. Potential reasons cited for this are time pressure, lack of expertise and poor access to specialists. AIM: To understand organisational factors and beliefs and behaviours among primary HCPs that may present barriers to identifying OA. METHODS: We employed a qualitative phenomenological methodology and undertook 20-45 min interviews with primary HCPs in West Midlands, UK. We used purposive and snowball sampling to include general practitioners (GPs) and practice nurses with a range of experience, from urban and rural settings. Interviews were recorded digitally and transcribed professionally for analysis. Data were coded by hand, and thematic analysis was undertaken and determined theoretically until themes were saturated. RESULTS: Eleven HCPs participated (eight GPs, three nurses). Four themes were identified that were considered to impact on identification of OA: (1) training and experience, (2) perceptions and beliefs, (3) systems constraints, and (4) variation in individual practice. OA-specific education had been inadequate at every stage of training and practice, and clinical exposure to OA had been generally limited. OA-specific beliefs varied, as did clinical behaviour with working-age individuals with asthma. There was a focus on diagnosis and treatment rather than attributing causation. Identified issues regarding organisation of asthma care were time constraints, lack of continuity, referral pressure, use of guidelines and templates, and external targets. CONCLUSION: Organisation and delivery of primary asthma care, negative OA-related beliefs, lack of formal education, and exposure to OA may all currently inhibit its identification.

Real world experience of response to pirfenidone in patients with idiopathic pulmonary fibrosis: a two centre retrospective study.

INTRODUCTION: Pirfenidone has been shown to reduce the decline in forced vital capacity (FVC) compared to placebo in patients with idiopathic pulmonary fibrosis (IPF). Previous studies have suggested that patients with a more rapid decline in FVC during the period before starting pirfenidone experience the greatest benefit from treatment. The purpose of this retrospective observational study was to investigate the response to pirfenidone in IPF patients, comparing two groups stratified by the annual rate of decline in FVC % predicted prior to treatment. METHODS: Using the rate of decline in FVC % predicted in the 12 months prior to pirfenidone, patients were stratified into slow (<5%) or rapid (≥5%) decliner groups. Comparisons in the lung function response to pirfenidone in these two groups were performed. RESULTS: Pirfenidone resulted in no statistically significant reduction in the median annual rate of decline in FVC or FVC % predicted. In the rapid decliners, pirfenidone significantly reduced the median (IQR) annual rate of decline in FVC % predicted (-8.7 (-14.2 - -7.0) %/yr vs 2.0 (-7.1 - 6.0) %/yr; n=17; p<0.01). In the slow decliners, pirfenidone did not reduce the median (IQR) annual rate of decline in FVC % predicted (-1.3 (-3.2 - 1.3) %/yr vs -5.0 (-8.3 - -0.35) %/yr; n=17; p=0.028). CONCLUSIONS: We demonstrate the greater net effect of pirfenidone in IPF patients declining rapidly. We suggest that using an annual rate of decline in FVC of <5% and ≥5% may be useful in counselling patients with regard to pirfenidone treatment. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 218-224).

Facilities for investigating occupational asthma in UK non-specialist respiratory departments.

BACKGROUND: The facilities which should be available to physicians offering specialist occupational asthma services have recently been agreed upon by a UK panel of experts. AIMS: This study aimed to investigate whether these facilities are available in UK non-specialist secondary care respiratory departments and to document tertiary care referral patterns. METHODS: A random sample of 100 UK respiratory units was selected, and the lead consultant invited to participate. Face-to-face interviews were conducted to document information on departmental facilities available for investigating cases of occupational asthma and utilization of tertiary referral centres. RESULTS: In total, 66% of consultants interviewed had seen a case of occupational asthma in the previous month, and 76% reported having ever referred a patient with suspected occupational asthma to a specialist centre for further investigation (referral distance range 1-111 miles). All the departments were able to perform the investigations previously deemed an absolute necessity in all patients. The availability of in-house facilities that were deemed as must be available varied between 3-100%. CONCLUSIONS: The results of this study demonstrate that while the majority of basic facilities are widely available, many respiratory departments do not have direct access to investigations routinely required to investigate occupational asthma. Access to specialist occupational respiratory centres varies within the UK, and in some parts of the country involves long travelling distances for patients.

Work-related asthma symptoms and attitudes to the workplace.

BACKGROUND: The Health & Safety Executive estimate that between 1500-3000 UK workers develop asthma through potentially avoidable workplace exposures each year. AIMS: To assess the perception of health, safety and the work environment by workers with symptoms suggestive of occupational asthma. METHODS: A total of 97 workers referred to hospital specialists with symptoms suggestive of occupational asthma were studied in order to investigate their attitudes to the workplace, safety and health. A qualitative study design using semi-structured telephone interviews at 2 months and 12 months following enrolment was used at 6 national UK centres with a special interest in occupational asthma. RESULTS: Many workers in the study felt let down by the workplace and management and perceived that a lack of health and safety measures had contributed to the development of their asthma symptoms. Many workers felt that their employers were 'uncaring' and were pursuing or considering medico-legal cases against them. CONCLUSIONS: Workers' perception of risk influences their behaviour in the workplace, and their own health beliefs potentially create barriers to changing this. It is essential to consider workers' perceptions when developing strategies to effect change within the workplace.