European Respiratory Journal最新文献

Background: Halm's clinical stability criteria have long guided antibiotic treatment and hospital discharge decisions for patients hospitalised with community-acquired pneumonia (CAP). Originally introduced in 1998, these criteria were established based on a relatively small and select patient population. Consequently, our study aims to reassess their applicability in the management of CAP in a contemporary real-world setting.

Methods: This cohort study included 2918 immunocompetent patients hospitalised with CAP from three hospitals in Denmark between 2017 and 2020. The primary outcome was time to achieve clinical stability as defined by Halm's criteria. Additionally, we examined recurrence of clinical instability and severe complications. Cumulative incidence function or Kaplan-Meier survival curves were used to analyse these outcomes, considering competing risks.

Results: The study population primarily comprised elderly individuals (median age 75 years) with significant comorbidities. The median time to clinical stability according to Halm's criteria was 4 days, with one-fifth experiencing recurrence of instability after early clinical response (stability within 3 days). Severe complications within 30 days mainly comprised mortality, with rates of 5.1% (64/1257) overall in those with early clinical response, 1.7% (18/1045) in the subgroup without do-not-resuscitate orders and 17.3% (276/1595) among the rest.

Conclusion: Halm's clinical stability criteria effectively classify CAP patients with different disease courses, yet achieving stability required more time in this ageing population with substantial comorbidities and more severe disease. Early clinical response indicates reduced risk of complications, especially in those without do-not-resuscitate orders.

Background: Computer-aided detection (CAD) systems hold promise for improving tuberculosis (TB) detection on digital chest radiographs. However, data on their performance in exclusively paediatric populations are scarce.

Methods: We conducted a retrospective diagnostic accuracy study evaluating the performance of CAD4TBv7 (Computer-Aided Detection for Tuberculosis version 7) using digital chest radiographs from well-characterised cohorts of Gambian children aged <15 years with presumed pulmonary TB. The children were consecutively recruited between 2012 and 2022. We measured CAD4TBv7 performance against a microbiological reference standard (MRS) of confirmed TB, and also performed Bayesian latent class analysis (LCA) to address the inherent limitations of the MRS in children. Diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUROC) and point estimates of sensitivity and specificity.

Results: A total of 724 children were included in the analysis, with confirmed TB in 58 (8%), unconfirmed TB in 145 (20%) and unlikely TB in 521 (72%). Using the MRS, CAD4TBv7 showed an AUROC of 0.70 (95% CI 0.60-0.79), and demonstrated sensitivity and specificity of 19.0% (95% CI 11-31%) and 99.0% (95% CI 98.0-100.0%), respectively. Applying Bayesian LCA with the assumption of conditional independence between tests, sensitivity and specificity estimates for CAD4TBv7 were 42.7% (95% CrI 29.2-57.5%) and 97.9% (95% CrI 96.6-98.8%), respectively. When allowing for conditional dependence between culture and Xpert assay, CAD4TBv7 demonstrated a sensitivity of 50.3% (95% CrI 32.9-70.0%) and specificity of 98.0% (95% CrI 96.7-98.9%).

Conclusion: Although CAD4TBv7 demonstrated high specificity, its suboptimal sensitivity underscores the crucial need for optimisation of CAD4TBv7 for detecting TB in children.

Background: Control of latent tuberculosis infection (LTBI) is a priority in the World Health Organization strategy to eliminate TB. Many high-income, low TB incidence countries have prioritised LTBI screening and treatment in recent migrants. We tested whether a novel model of care, based entirely within primary care, was effective and safe compared to secondary care.

Methods: This was a pragmatic cluster-randomised, parallel group, superiority trial (ClinicalTrials.gov: NCT03069807) conducted in 34 general practices in London, UK, comparing LTBI treatment in recent migrants in primary care to secondary care. The primary outcome was treatment completion, defined as taking ≥90% of antibiotic doses. Secondary outcomes included treatment acceptance, adherence, adverse effects, patient satisfaction, TB incidence and a cost-effectiveness analysis. Analyses were performed on an intention-to-treat basis.

Results: Between September 2016 and May 2019, 362 recent migrants with LTBI were offered treatment and 276 accepted. Treatment completion was similar in primary and secondary care (82.6% versus 86.0%; adjusted OR (aOR) 0.64, 95% CI 0.31-1.29). There was no difference in drug-induced liver injury between primary and secondary care (0.7% versus 2.3%; aOR 0.29, 95% CI 0.03-2.84). Treatment acceptance was lower in primary care (65.2% (146/224) versus 94.2% (130/138); aOR 0.10, 95% CI 0.03-0.30). The estimated cost per patient completing treatment was lower in primary care, with an incremental saving of GBP 315.27 (95% CI 313.47-317.07).

Conclusions: The treatment of LTBI in recent migrants within primary care does not result in higher rates of treatment completion but is safe and costs less when compared to secondary care.

Background: Idiopathic pulmonary fibrosis (IPF) carries a high risk of lung cancer, but the effect of pirfenidone on lung cancer development remains uncertain. We investigated the association between pirfenidone use and lung cancer development in patients with IPF.

Methods: We included 10 084 patients with IPF from the national claims database. Propensity score analysis with inverse probability of treatment weighting (IPTW) and landmark analyses were employed to evaluate lung cancer occurrence according to pirfenidone use. The association was evaluated using Cox regression models adjusted for clinical and socioeconomic variables. A single-center IPF clinical cohort (n=941) was used for validating the findings.

Results: The mean patient age was 69.4 years, 73.8% were men, and 31.6% received pirfenidone. Lung cancer developed in 766 patients with IPF (7.6%; 21.9 cases per 1000 person-years) during a median follow-up of 3.0 years. After IPTW, the pirfenidone group showed lower incidence (10.4 versus 27.9 cases per 1000 person-years) than the no-pirfenidone group. Landmark analysis at 6 months after IPF diagnosis also showed lower incidence of lung cancer in the pirfenidone group than in the no-pirfenidone group. Pirfenidone use was independently associated with a reduced lung cancer risk (weighted adjusted hazard ratio [HR]: 0.347; 95% confidence interval [CI]: 0.258-0.466). A clinical cohort showed similar association (weighted adjusted HR: 0.716; 95% CI: 0.517-0.991). The association persisted across subgroups defined by age or sex.

Conclusion: Pirfenidone use may be associated with a reduced lung cancer risk in patients with IPF.

Background: Pseudomonas aeruginosa is a common pathogen that contributes to progressive lung disease in cystic fibrosis (CF). Genetic factors other than CF-causing CFTR (CF transmembrane conductance regulator) variations contribute ∼85% of the variation in chronic P. aeruginosa infection age in CF according to twin studies, but the susceptibility loci remain unknown. Our objective is to advance understanding of the genetic basis of host susceptibility to P. aeruginosa infection.

Materials and methods: We conducted a genome-wide association study of chronic P. aeruginosa infection age in 1037 Canadians with CF. We subsequently assessed the genetic correlation between chronic P. aeruginosa infection age and lung function through polygenic risk score (PRS) analysis and inferred their causal relationship through bidirectional Mendelian randomisation analysis.

Results: Two novel genome-wide significant loci with lead single nucleotide polymorphisms (SNPs) rs62369766 (chr5p12; p=1.98×10^-8) and rs927553 (chr13q12.12; p=1.91×10^-8) were associated with chronic P. aeruginosa infection age. The rs62369766 locus was validated using an independent French cohort (n=501). Furthermore, the PRS constructed from CF lung function-associated SNPs was significantly associated with chronic P. aeruginosa infection age (p=0.002). Finally, our analysis presented evidence for a causal effect of lung function on chronic P. aeruginosa infection age (β=0.782 years, p=4.24×10^-4). In the reverse direction, we observed a moderate effect (β=0.002, p=0.012).

Conclusions: We identified two novel loci that are associated with chronic P. aeruginosa infection age in individuals with CF. Additionally, we provided evidence of common genetic contributors and a potential causal relationship between P. aeruginosa infection susceptibility and lung function in CF. Therapeutics targeting these genetic factors may delay the onset of chronic infections, which account for significant remaining morbidity in CF.

Background: Exercise pulmonary hypertension (ePH), defined as a mean pulmonary artery pressure (mPAP)/cardiac output (Qc) slope >3 WU during exercise, is common in patients with heart failure with preserved ejection fraction (HFpEF). However, the pulmonary gas exchange-related effects of an exaggerated ePH (EePH) response are not well-defined, especially in relation to dyspnea on exertion (DOE) and exercise intolerance.

Methods: 48 HFpEF patients underwent invasive (pulmonary and radial artery catheters) constant-load (20W) and maximal incremental cycle testing. Hemodynamic measurements (mPAP and Qc), arterial blood and expired gases, and ratings of breathlessness (RPB, Borg 0-10) were obtained. The mPAP/Qc slope was calculated from rest-to-20W. Those with a mPAP/Qc slope >4.2 (median) were classified as HFpEF+EePH (n=24) and those with a mPAP/Qc slope <4.2 were classified as HFpEF (without EePH) (n=24). The A-aDO₂, V_D/V_T (Bohr equation), and the V_E/VCO₂ slope (from rest-to-20W) were calculated.

Results: PaO₂ was lower (p=0.03), and V_D/V_T was higher (p=0.03) at peak exercise in HFpEF+EePH compared with HFpEF. A-aDO₂ was similar at peak exercise between groups (p=0.14); however, HFpEF+EePH achieved the peak A-aDO₂ at a lower peak work rate (p<0.01). The V_E/VCO₂ slope was higher in HFpEF+EePH compared with HFpEF (p=0.01). RPB was ≥1-unit higher at 20W and VO_2peak was lower (p<0.01) in HFpEF+EePH compared with HFpEF.

Conclusions: These data suggest that EePH contributes to pulmonary gas exchange impairments during exercise by causing a V/Q mismatch that provokes both ventilatory inefficiency and hypoxemia, both of which seem to contribute to DOE and exercise intolerance in patients with HFpEF.

Background: Drug-induced interstitial lung disease (DI-ILD) is a heterogeneous subgroup of interstitial lung diseases (ILD). The number of molecules involved is increasing with time. Due to their low incidence, DI-ILDs may be detected only after a drug has been marketed, notably through Adverse Drug Reaction (ADR) reports to pharmacovigilance centres. The aim of our study was to describe drug-induced diffuse lung disease cases notified to and recorded by the French Pharmacovigilance Database (FPVD), reported clinical pictures and the potentially causal drugs.

Methods: This retrospective study included cases registered in the FPVD from 1st January 1985 to 1st April 2022 which had ADR coded in MedDRA with a High Level Group Term "Lower respiratory tract disorders (excluding obstruction and infection)" involving patients aged 18 and over.

Results: We analysed 7234 cases involving 13 059 suspect medications and 1112 specific molecules. Cases were categorised as serious in 96.7% and in 13.3% death ensued. Men accounted for 54.4% of the cases. Median age was 69 [18-103] years. The most prevalent ADRs were "ILD" (51.0%), "Pulmonary oedema" (acute/non-acute) (15.6%) and "Pulmonary fibrosis" (10.5%). "Anti-cancer drugs" (31.2%) and "Cardiovascular drugs" (29.1%) were the most prominent therapeutic classes involved, with amiodarone being the most commonly reported suspected drug (10.0%), followed by methotrexate (3.1%).

Conclusion: This study from a large nationwide dataset spanning 37 years is the largest known to date. Drug-induced diffuse lung diseases are serious with a potentially fatal outcome. Accurate diagnoses remain essential to identify it properly and discontinue the culprit drug urgently.

The global impacts of pulmonary hypertension (PH) were formally recognised in 1973 at the 1st World Health Organization meeting dedicated to primary pulmonary hypertension, held in Geneva. Investigations into disease pathogenesis and classification led to the development of numerous therapies over the ensuing decades. While the impacts of the disease have been lessened due to treatments, the symptoms and adverse effects of PH and its therapies on patients' wellbeing and mental health remain significant. As such, there is a critical need to enhance understanding of the challenges patients face on a global scale with respect to care access, multidimensional patient support and advocacy. In addition, thoughtful analysis of the potential benefits and utilisation of mechanisms for the incorporation of patient-reported outcomes into diagnosis and treatment plans is needed. A summary of these areas is included here. We present a report of global surveys of patient and provider experiences and challenges regarding care access and discuss possible solutions. Also addressed is the current state of PH patient associations around the world. Potential ways to enhance patient associations and enable them to provide the utmost support are discussed. A summary of relevant patient-reported outcome measures to assess health-related quality of life in PH is presented, with suggestions regarding incorporation of these tools in patient care and research. Finally, information on how current global threats such as pandemics, climate change and armed conflict may impact PH patients is offered, along with insights as to how they may be mitigated with advanced contingency planning.