Patients with idiopathic pulmonary fibrosis (IPF) frequently have a substantial burden of comorbidities [1]. Antifibrotic therapy is recommended to slow the progression of IPF [2]. Patients receiving antifibrotic therapy frequently receive concomitant medications for the management of comorbidities [1, 3–9]. Previous post hoc analyses of antacids, statins, metformin, anticoagulants and angiotensin modulators in patients with IPF enrolled in phase III randomised controlled trials (RCTs) have generated hypotheses on the impact of these treatments on IPF outcomes [3–9]. The effects of multiple concomitant medications in patients with IPF have been largely unexplored. The objective of the present analyses was to explore the association between use of combinations of frequently prescribed concomitant medications and disease outcomes in patients with IPF.

Rationale Precapillary pulmonary hypertension (PH) is a devastating complication of sickle cell disease (SCD). Little is known about the influence of the SCD genotype on PH characteristics. Objectives To describe clinical phenotypes and outcomes of precapillary PH due to SCD according to disease genotype. Methods A nationwide multicentre retrospective study including all patients with SCD-related precapillary PH from the French PH Registry was conducted. Clinical characteristics and outcomes according to SCD genotype were analysed. Results 58 consecutive SCD patients with precapillary PH were identified, of whom 41 had homozygous for haemoglobin S (SS) SCD, three had S-β 0 thalassaemia (S-β 0 thal) and 14 had haemoglobin SC disease (SC). Compared to SC patients, SS/S-β 0 thal patients were characterised by lower 6-min walk distance (p=0.01) and lower pulmonary vascular resistance (p=0.04). Mismatched segmental perfusion defects on lung scintigraphy were detected in 85% of SC patients and 9% of SS/S-β 0 thal patients, respectively, and 50% of SS/S-β 0 thal patients had heterogeneous lung perfusion without segmental defects. After PH diagnosis, 31 patients (53%) received medical therapies approved for pulmonary arterial hypertension, and chronic red blood cell exchange was initiated in 23 patients (40%). Four patients were managed for chronic thromboembolic PH by pulmonary endarterectomy (n=1) or balloon pulmonary angioplasty (n=3). Overall survival was 91%, 80% and 60% at 1, 3 and 5 years, respectively, without influence of genotype on prognosis. Conclusions Patients with precapillary PH related to SCD have a poor prognosis. Thrombotic lesions appear as a major component of PH related to SCD, more frequently in SC patients.

Sarcoidosis is a complex disease characterised by the presence of epithelioid non-caseating granulomatous inflammation affecting multiple organs and whose aetiology has been related to microbial, environmental and genetic factors [1, 2]. However, no single antigenic trigger has been identified, although associations with Propionibacterium acnes and mycobacteria pathogen-associated molecular pattern, deposition of serum amyloid A, and exposure to inorganic particles and insecticides have been suggested [3–5]. Occurrence of familial cases suggests that genetic variation contributes to disease pathogenesis with a heritability of about 39% [6]. Despite intensive genome-wide association studies, no single nucleotide polymorphism is, as yet, able to explain the “missing heritability” in the disease, especially for non-resolving, non-Löfgren syndrome sarcoidosis .We read with interest the research letter by REINIKOVAITE et al. [1], in which the authors reported same level of damage in the lungs of Sprague Dawley rats subjected to whole body chronic exposure of e-cigarette vapour emissions and cigarette smoke, as well as to subcutaneous injection of nicotine. Their conclusion is that e-cigarette use and long-time consumption of nicotine are just as toxic as tobacco cigarettes. We appreciate the authors’ intention to address concerns related to the potential long-term health effects of e-cigarette use and nicotine exposure, but there are a number of methodological considerations that lessen the impact of their findings.

Background Data from the INMARK trial were used to investigate the feasibility and validity of home spirometry as a measure of lung function decline in patients with idiopathic pulmonary fibrosis (IPF). Methods Subjects with IPF and preserved forced vital capacity (FVC) were randomised to receive nintedanib or placebo for 12 weeks followed by open-label nintedanib for 40 weeks. Clinic spirometry was conducted at baseline and weeks 4, 8, 12, 16, 20, 24, 36 and 52. Subjects were asked to perform home spirometry at least once a week and ideally daily. Correlations between home- and clinic-measured FVC and rates of change in FVC were assessed using Pearson correlation coefficients. Results In total, 346 subjects were treated. Mean adherence to weekly home spirometry decreased over time but remained above 75% in every 4-week period. Over 52 weeks, mean adherence was 86%. Variability in change from baseline in FVC was greater when measured by home rather than clinic spirometry. Strong correlations were observed between home- and clinic-measured FVC at all time-points (r=0.72–0.84), but correlations between home- and clinic-measured rates of change in FVC were weak (r=0.26 for rate of decline in FVC over 52 weeks). Conclusion Home spirometry was a feasible and valid measure of lung function in patients with IPF and preserved FVC, but estimates of the rate of FVC decline obtained using home spirometry were poorly correlated with those based on clinic spirometry.

We used data from the INBUILD and INPULSIS trials to investigate the natural history of progressive fibrosing interstitial lung diseases (ILDs). Subjects in the two INPULSIS trials had a clinical diagnosis of idiopathic pulmonary fibrosis (IPF) while subjects in the INBUILD trial had a progressive fibrosing ILD other than IPF and met protocol-defined criteria for ILD progression despite management. Using data from the placebo groups, we compared the rate of decline in forced vital capacity (FVC) (mL·year −1 ) and mortality over 52 weeks in the INBUILD trial with pooled data from the INPULSIS trials. The adjusted mean annual rate of decline in FVC in the INBUILD trial (n=331) was similar to that observed in the INPULSIS trials (n=423) (−192.9 mL·year −1 and −221.0 mL·year −1 , respectively; nominal p-value=0.19). The proportion of subjects who had a relative decline in FVC >10% predicted at Week 52 was 48.9% in the INBUILD trial and 48.7% in the INPULSIS trials, and the proportion who died over 52 weeks was 5.1% in the INBUILD trial and 7.8% in the INPULSIS trials. A relative decline in FVC >10% predicted was associated with an increased risk of death in the INBUILD trial (hazard ratio 3.64) and the INPULSIS trials (hazard ratio 3.95). These findings indicate that patients with fibrosing ILDs other than IPF, who are progressing despite management, have a subsequent clinical course similar to patients with untreated IPF, with a high risk of further ILD progression and early mortality.

Systemic sclerosis (SSc) is a systemic autoimmune disease affecting multiple organ systems, including the lungs. Interstitial lung disease (ILD) is the leading cause of death in SSc. There are no valid biomarkers to predict the occurrence of SSc-ILD, although auto-antibodies against anti-topoisomerase I and several inflammatory markers are candidate biomarkers that need further evaluation. Chest auscultation, presence of shortness of breath and pulmonary function testing are important diagnostic tools, but lack sensitivity to detect early ILD. Baseline screening with high-resolution computed tomography (HRCT) is therefore necessary to confirm an SSc-ILD diagnosis. Once diagnosed with SSc-ILD, patients' clinical courses are variable and difficult to predict, although certain patient characteristics and biomarkers are associated with disease progression. It is important to monitor patients with SSc-ILD for signs of disease progression, although there is no consensus about which diagnostic tools to use or how often monitoring should occur. In this article, we review methods used to define and predict disease progression in SSc-ILD. There is no valid definition of SSc-ILD disease progression, but we suggest that either a decline in forced vital capacity (FVC) from baseline of ≥10%, or a decline in FVC of 5–9% in association with a decline in diffusing capacity of the lung for carbon monoxide of ≥15% represents progression. An increase in the radiographic extent of ILD on HRCT imaging would also signify progression. A time period of 1–2 years is generally used for this definition, but a decline over a longer time period may also reflect clinically relevant disease progression.