The impact of air pollution on interstitial lung disease: a systematic review and meta-analysis

IntroductionThere is a growing body of evidence suggesting a causal relationship between interstitial lung disease (ILD) and air pollution, both for the development of the disease, and driving disease progression. We aim to provide a comprehensive literature review of the association between air pollution, and ILD, including idiopathic pulmonary fibrosis (IPF).MethodsWe systematically searched from six online database. Two independent authors (DL and CF) selected studies and critically appraised the risk of bias using the Newcastle-Ottawa Scale (NOS). Findings are presented through a narrative synthesis and meta-analysis. Meta-analyses were performed exclusively when there was a minimum of three studies examining identical pollutant-health outcome pairs, all evaluating equivalent increments in pollutant concentration, using a random effects model.Results24 observational studies conducted in 13 countries or regions were identified. Pollutants under investigation encompassed ozone (O3), nitrogen dioxide (NO2), Particulate matter with diameters of 10 micrometers or less (PM10) and 2.5 micrometers or less (PM2.5), sulfur dioxide (SO2), carbon monoxide (CO), nitric oxide (NO) and nitrogen oxides (NOx). We conducted meta-analyses to assess the estimated Risk Ratios (RRs) for acute exacerbations (AE)-IPF in relation to exposure to every 10 μg/m3 increment in air pollutant concentrations, including O3, NO2, PM10, and PM2.5. The meta-analysis revealed a significant association between the increased risk of AE-IPF in PM2.5, yielding RR 1.94 (95% CI 1.30–2.90; p = 0.001). Findings across all the included studies suggest that increased exposure to air pollutants may be linked to a range of health issues in individuals with ILDs.ConclusionA scarcity of available studies on the air pollutants and ILD relationship underscores the imperative for further comprehensive research in this domain. The available data suggest that reducing levels of PM2.5 in the atmosphere could potentially reduce AE frequency and severity in ILD patients

Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: design of a double-blind, randomised, placebo-controlled phase II trial

Introduction: Despite extensive multidisciplinary team (MDT) assessment, some patients have interstitial lung disease (ILD) that is considered unclassifiable (uILD), for which there are currently no approved treatments. This study will assess the efficacy and safety of the antifibrotic pirfenidone in treating uILD. Methods and analysis: This double-blind, randomised, placebo-controlled phase II trial is enrolling adults with fibrosing ILD, including uILD that fulfils proposed research criteria for interstitial pneumonia with autoimmune features (IPAF), that cannot be classified with moderate or high confidence to any category of ILD following MDT discussion. Study participants must have >10% fibrosis on high-resolution CT scan within the previous 12 months, forced vital capacity (FVC) ≥45% and diffusing capacity of the lung for carbon monoxide ≥30% of predicted values. Study participants will be randomised to receive 801 mg pirfenidone or placebo three times daily for 24 weeks. The efficacy of pirfenidone vs placebo will be assessed by daily measurement of FVC using a handheld spirometer over the treatment period. Other functional parameters, patient-reported outcomes, samples for biomarker analysis and safety endpoints will be collected. Additionally, the study will assess the efficacy and safety of pirfenidone with and without concomitant mycophenolate mofetil treatment and in study participants with or without IPAF. Ethics and dissemination: This trial is being conducted in accordance with the International Conference on Harmonisation E6 guideline for Good Clinical Practice, Declaration of Helsinki and local laws for countries in which the research is conducted

Cardiovascular safety of nintedanib in subgroups by cardiovascular risk at baseline in the TOMORROW and INPULSIS trials

Nintedanib is a tyrosine kinase inhibitor used to treat idiopathic pulmonary fibrosis (IPF). We investigated the cardiovascular safety of nintedanib using pooled data from the TOMORROW and INPULSIS trials.Cardiovascular events were assessed post hoc in patients with a history of atherosclerotic cardiovascular disease (CVD) and/or one or more cardiovascular risk factors at baseline ("higher cardiovascular risk") and patients with no history of atherosclerotic CVD and no cardiovascular risk factors at baseline ("lower cardiovascular risk").Incidence rates were calculated for 1231 patients (n=723 nintedanib and n=508 placebo), of whom 89.9% had higher cardiovascular risk. Incidence rates of major adverse cardiovascular events were similar in the nintedanib and placebo groups in patients with higher cardiovascular risk (3.88 (95% CI 2.58-5.84) and 3.49 (95% CI 2.10-5.79) per 100 patient-years, respectively) and lower cardiovascular risk (4.78 (95% CI 1.54-14.82) and 5.37 (95% CI 1.73-16.65) per 100 patient-years, respectively). Incidence rates of myocardial infarction in the nintedanib and placebo groups, respectively, were 3.03 (95% CI 1.91-4.81) and 1.16 (95% CI 0.48-2.79) per 100 patient-years in patients with higher cardiovascular risk and 1.59 (95% CI 0.22-11.29) and 1.78 (95% CI 0.25-12.64) per 100 patient-years in patients with lower cardiovascular risk. Incidence rates of other ischaemic heart disease in the nintedanib and placebo groups, respectively, were 1.85 (95% CI 1.02-3.34) and 3.28 (95% CI 1.94-5.54) per 100 patient-years in patients with higher cardiovascular risk and 0 and 1.80 (95% CI 0.25-12.78) per 100 patient-years in patients with lower cardiovascular risk.These data help to establish the cardiovascular safety profile of nintedanib in IPF

Patient Registries in Idiopathic Pulmonary Fibrosis.

Over the past decade, several large registries of patients with idiopathic pulmonary fibrosis (IPF) have been established. These registries are collecting a wealth of longitudinal data on thousands of patients with this rare disease. The data collected in these registries will be complementary to data collected in clinical trials because the patient populations studied in registries have a broader spectrum of disease severity and comorbidities and can be followed for a longer period of time. Maintaining the quality and completeness of registry databases presents administrative and resourcing challenges, but it is important to ensuring the robustness of the analyses. Data from patient registries have already helped improve understanding of the clinical characteristics of patients with IPF, the impact that the disease has on their quality of life and survival, and current practices in diagnosis and management. In the future, analyses of biospecimens linked to detailed patient profiles will provide the opportunity to identify biomarkers linked to disease progression, facilitating the development of precision medicine approaches for prognosis and therapy in patients with IPF

An empirical approach to the nucleation of sulfuric acid droplets in the atmosphere

We use quantum mechanical evaluations of the Gibbs free energy of the hydrates of sulfuric acid, H2SO4. nH2O and (H2SO4)2 . nH2O to evaluate an empirical surface tension for sulfuric acid-water clusters containing few molecules. We use this surface tension to evaluate nucleation rates using classical heteromolecular theory. At low temperatures (T 213 K) the nucleation rates obtained with the empirical surface tensions are signifi cantly greater than those using bulk values of the surface tension. At higher temperatures the difference disappears

Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: An international case-cohort study

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts.A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (κw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the C-index.A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (κw=0.65, IQR 0.53–0.72, p less than 0.0001) or physicians with access to multidisciplinary team (MDT) meetings (κw=0.54, IQR 0.45–0.64, p less than 0.0001). The prognostic accuracy of academic physicians with greater than 20 years of experience (C-index=0.72, IQR 0.0–0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70–0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72–0.75).Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts

Integrating Clinical Probability into the Diagnostic Approach to Idiopathic Pulmonary Fibrosis: An International Working Group Perspective

Background. When considering the diagnosis of idiopathic pulmonary fibrosis (IPF), experienced clinicians integrate clinical features that help to differentiate IPF from other fibrosing interstitial lung diseases, thus generating a “pre-test” probability of IPF. The aim of this international working group perspective was to summarize these features using a tabulated approach similar to chest HRCT and histopathologic patterns reported in the international guidelines for the diagnosis of IPF, and to help formally incorporate these clinical likelihoods into diagnostic reasoning to facilitate the diagnosis of IPF. Methods. The committee group identified factors that influence the clinical likelihood of a diagnosis of IPF, which was categorized as a pre-test clinical probability of IPF into “high” (70-100%), “intermediate” (30-70%), or “low” (0-30%). After integration of radiological and histopathological features, the post-test probability of diagnosis was categorized into “definite” (90-100%), “high confidence” (70-89%), “low confidence” (51-69%), or “low” (0-50%) probability of IPF. Findings. A conceptual Bayesian framework was created, integrating the clinical likelihood of IPF (“pre-test probability of IPF”) with the HRCT pattern, the histopathology pattern when available, and/or the pattern of observed disease behavior into a “post-test probability of IPF”. The diagnostic probability of IPF was expressed using an adapted diagnostic ontology for fibrotic interstitial lung diseases. Interpretation. The present approach will help incorporate the clinical judgement into the diagnosis of IPF, thus facilitating the application of IPF diagnostic guidelines and, ultimately improving diagnostic confidence and reducing the need for invasive diagnostic techniques