ERJ Open Research最新文献

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF, and a prior association of the HLA-DQB1 gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Owing to the important role that the human leukocyte antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk.

Methods: We performed a meta-analysis of associations of the HLA region with IPF risk in individuals of European ancestry from seven independent case-control studies of IPF (comprising 5159 cases and 27 459 controls, including a prior study of fibrotic interstitial pneumonia). Single nucleotide polymorphisms, classical HLA alleles and amino acids were analysed and signals meeting a region-wide association threshold of p<4.5×10^-4 and a posterior probability of replication >90% were considered significant. We sought to replicate the previously reported HLA-DQB1 association in the subset of studies independent of the original report.

Results: The meta-analysis of all seven studies identified four significant independent single nucleotide polymorphisms associated with IPF risk. However, none met the posterior probability for replication criterion. The HLA-DQB1 association was not replicated in the independent IPF studies.

Conclusion: Variation in the HLA region was not consistently associated with risk in studies of IPF. However, this does not preclude the possibility that other genomic regions linked to the immune response may be involved in the aetiology of IPF.

Background: Our objective was to evaluate the short-, medium- and long-term benefits of home-based pulmonary rehabilitation (PR) on the physical and affective components of dyspnoea in people with fibrotic idiopathic interstitial pneumonias (f-IIPs). Anxiety and depressive symptoms, fatigue, health-related quality of life and exercise tolerance were also assessed.

Methods: Data on 166 individuals with f-IIPs who enrolled in an 8-week home-based PR programme (weekly supervised 90-min session) were retrospectively analysed. Assessments included the Dyspnoea-12 (D-12) questionnaire, Hospital Anxiety and Depression Scale, Fatigue Assessment Scale, Visual Simplified Respiratory Questionnaire and 6-min stepper test, and were performed at home at short, medium (6 months) and long (12 months) term.

Results: Among the 166 individuals with f-IIPs who enrolled in PR, 75 (45%) and 91 (55%) participants had a diagnosis of idiopathic pulmonary fibrosis and fibrosing non-specific interstitial pneumonia, respectively, and 87 (52%) participants concluded a full year of follow-up. In the total group, both physical and affective components of dyspnoea were improved, at short, medium and long term, after PR. Overall, half of the participants reached the minimally important difference of 3 points of the D-12 questionnaire at the end of PR, and at the 6- and 12-month follow-ups. Anxiety and depressive symptoms, fatigue and health-related quality of life were also improved, while the short-term benefits in exercise tolerance were not maintained 1 year after PR.

Conclusion: An individualised home-based PR programme resulted in short-, medium- and long-term improvements in both physical and affective components of dyspnoea assessed by the D-12 questionnaire.

Nocturnal hypoxia has a significant impact on prognosis in patients with fibrotic interstitial lung diseases https://bit.ly/3RNzNVu.

Background: Not all hypercapnic COPD patients benefit from home noninvasive ventilation (NIV), and mechanisms through which NIV improves clinical outcomes remain uncertain. We aimed to identify "responders" to home NIV, denoted by a beneficial effect of NIV on arterial partial pressure of carbon dioxide (P_aCO2), health-related quality of life (HRQoL) and survival, and investigated whether NIV achieves its beneficial effect through an improved P_aCO2.

Methods: We used individual patient data from previous published trials collated for a systematic review. Linear mixed-effect models were conducted to compare the effect of NIV on P_aCO2, HRQoL and survival, within subgroups defined by patient and treatment characteristics. Secondly, we conducted a causal mediation analysis to investigate whether the effect of NIV is mediated by a change in P_aCO2.

Findings: Data of 1142 participants from 16 studies were used. Participants treated with lower pressure support (<14 versus ≥14 cmH₂O) and with lower adherence (<5 versus ≥5 h·day^-1) had less improvement in P_aCO2 (mean difference (MD) -0.30 kPa, p<0.001 and -0.29 kPa, p<0.001, respectively) and HRQoL (standardised MD 0.10, p=0.002 and 0.11, p=0.02, respectively), but this effect did not persist to survival. P_aCO2 improved more in patients with severe dyspnoea (MD -0.30, p=0.02), and HRQoL improved only in participants with fewer than three exacerbations (standardised MD 0.52, p=0.03). The results of the mediation analysis showed that the effect on HRQoL is mediated partially (23%) by a change in P_aCO2.

Interpretation: With greater pressure support and better daily NIV usage, a larger improvement in P_aCO2 and HRQoL is achieved. Importantly, we demonstrated that the beneficial effect of home NIV on HRQoL is only partially mediated through a reduction in diurnal P_aCO2.

Background: The determinants and health outcomes of lung function trajectories in adults among the general population are poorly understood. We aimed to identify and characterise clusters of lung function trajectories in adults aged ≥45 years.

Methods: Gaussian finite-mixture modelling was applied to baseline and annualised change of forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC) and FEV₁/FVC ratio z-scores in participants of the Rotterdam Study, a prospective population-based cohort study, with repeated spirometry (n=3884; mean±sd age 64.7±8.9 years). Longitudinal outcomes were all-cause mortality, respiratory outcomes (symptoms, COPD (FEV₁/FVC <0.7 in absence of asthma), preserved ratio impaired spirometry (PRISm; FEV₁/FVC ≥0.7 and FEV₁ or FVC <80%)), smoking cessation and weight changes. Independent risk factors, including genetics, were identified by multiple logistic regression.

Results: We identified eight trajectory clusters, with the reference group having persistently normal spirometry (prevalence 42.8%). Three clusters showed higher mortality, adjusted for confounders: 1) the persistently low FEV₁ cluster (prevalence 6.8%, hazard ratio (HR) 1.71, 95% CI 1.37-2.13); 2) rapid FEV₁ decliners (prevalence 4.6%, HR 1.48, 95% CI 1.10-1.99); and 3) FVC decliners (prevalence 3.7%, HR 1.49, 95% CI 1.09-2.03). In contrast, FVC improvers (prevalence 6.7%, HR 0.61, 95% CI 0.41-0.90) and persistently high FEV₁ (prevalence 29.2%, HR 0.82, 95% CI 0.69-0.98) were protective trajectory clusters. Clusters were characterised by differences in genetic predisposition (polygenic scores of FEV₁ and FEV₁/FVC), demographics, cigarette smoking, respiratory symptoms (chronic cough, wheezing and dyspnoea), cardiovascular factors (body mass index, hypertension and heart failure) and serum C-reactive protein levels. Frailty, weight changes and the development of respiratory symptoms, COPD and PRISm were significantly associated with trajectory clusters.

Conclusions: This study reveals clinically relevant lung function trajectory clusters in older adults of the general population.

[This corrects the article DOI: 10.1183/23120541.00239-2022.].

Background: Pulmonary hypertension (PH) leads to increased morbidity and mortality in interstitial lung disease (ILD). While the INCREASE trial highlighted the use of inhaled prostacyclin in PH-ILD patients, such therapy may be inadequate when right ventricular failure (RVF) is also present. In this study, we report the use of intravenous prostacyclin in three PH-ILD patients to stabilise right ventricular (RV) function, with a subsequent transition to maintenance therapy with inhaled prostacyclin.

Methods: We evaluated three consecutive PH-ILD patients with RVF. RV afterload and pulmonary vascular resistance (PVR) were treated with intravenous prostacyclin during the induction phase of the therapy. Patients transitioned from intravenous prostacyclin to the maintenance phase of the treatment with inhaled prostacyclin once three transition criteria were met: cardiac index (CI) >2 L·min^-1·m^-2, PVR <7 Wood units (WU) and tricuspid annular plane systolic excursion (TAPSE) change >1 mm or TAPSE >1.6 cm.

Results: Pre-treatment parameters for the three patients were a mean PVR of 14.3 WU, a mean Fick CI of 1.8 L·min^-1·m^-2 and a mean TAPSE of 1.4 cm. The average intravenous prostacyclin dose at the time of transition to maintenance therapy was 20.7 ng·kg^-1·m^-2 of treprostinil. At 3-months follow-up, the mean PVR was 6.3 WU, Fick CI 2.2 L·min^-1·m^-2 and TAPSE 1.7 cm.

Conclusion: This case series of three PH-ILD patients with RVF introduces the concept of an initial intravenous prostacyclin induction phase, followed by a transition to maintenance therapy with inhaled prostacyclin. Further development of this treatment algorithm with a refinement of the transition criteria, potential testing in a clinical trial and a longer-term follow-up period is warranted to improve the outcomes of advanced PH-ILD patients with concomitant RVF.

Introduction: Non-small cell lung cancer (NSCLC) is often associated with compromised lung function. Real-world data on the impact of surgical approach in NSCLC patients with compromised lung function are still lacking. The objective of this study is to assess the potential impact of minimally invasive surgery (MIS) on 90-day post-operative mortality after anatomic lung resection in high-risk operable NSCLC patients.

Methods: We conducted a retrospective multicentre study including all patients who underwent anatomic lung resection between January 2010 and October 2021 and registered in the Epithor database. High-risk patients were defined as those with a forced expiratory volume in 1 s (FEV₁) or diffusing capacity of the lung for carbon monoxide (D_LCO) value below 50%. Co-primary end-points were the impact of risk status on 90-day mortality and the impact of MIS on 90-day mortality in high-risk patients.

Results: Of the 46 909 patients who met the inclusion criteria, 42 214 patients (90%) with both preoperative FEV₁ and D_LCO above 50% were included in the low-risk group, and 4695 patients (10%) with preoperative FEV₁ and/or preoperative D_LCO below 50% were included in the high-risk group. The 90-day mortality rate was significantly higher in the high-risk group compared to the low-risk group (280 (5.96%) versus 1301 (3.18%); p<0.0001). In high-risk patients, MIS was associated with lower 90-day mortality compared to open surgery in univariate analysis (OR=0.04 (0.02-0.05), p<0.001) and in multivariable analysis after propensity score matching (OR=0.46 (0.30-0.69), p<0.001). High-risk patients operated through MIS had a similar 90-day mortality rate compared to low-risk patients in general (3.10% versus 3.18% respectively).

Conclusion: By examining the impact of surgical approaches on 90-day mortality using a nationwide database, we found that either preoperative FEV₁ or D_LCO below 50% is associated with higher 90-day mortality, which can be reduced by using minimally invasive surgical approaches. High-risk patients operated through MIS have a similar 90-day mortality rate as low-risk patients.

Background: Moderate-to-late preterm birth (32 to <37 weeks of gestation) has been associated with impaired lung function in adolescence, but data in adulthood and physiological phenotyping beyond spirometry are scarce. We aimed to investigate lung function development from adolescence into young adulthood and to provide physiological phenotyping in individuals born moderate-to-late preterm.

Methods: Lung function data from individuals born moderate-to-late preterm (n=110) and term (37 to <42 weeks of gestation, n=1895) in the Swedish birth cohort BAMSE were used for analysis and included dynamic spirometry, fractional exhaled nitric oxide and multiple breath nitrogen wash-out. Data from 16- and 24-year follow-ups were analysed using regression models stratified on sex and adjusted for smoking. Data-driven latent class analysis was used to phenotype moderate-to-late preterm individuals at 24 years, and groups were related to background factors.

Results: Males born moderate-to-late preterm had lower forced expiratory volume in 1 s (FEV₁) at 24 years of age (-0.28 z-score, p=0.045), compared to males born term. In females, no difference was seen at 24 years, partly explained by a significant catch up in FEV₁ between 16 and 24 years (0.18 z-score, p=0.01). Lung function phenotypes described as "asthma-like", "dysanapsis-like" and "preterm reference" were identified within the preterm group. Maternal overweight in early pregnancy was associated with "asthma-like" group membership (OR 3.59, p=0.02).

Conclusion: Our results show impaired FEV₁ at peak lung function in males born moderate-to-late preterm, while females born moderate-to-late preterm had significant catch up between the ages of 16 and 24 years. Several phenotypes of lung function impairment exist in individuals born moderate-to-late preterm.

Current smoking reduces small airway intraepithelial eosinophil counts in COPD patients and controls. This provides evidence of an attenuation of type-2 related inflammation in the small airways imposed by current smoking, which may affect ICS response. https://bit.ly/49YSKwG.