Respiratory medicine最新文献

Background

Phenotype classification contributes to risk assessment of asthma. Previous studies have applied this concept primarily to adult populations and in the setting of research protocol assessments which may not be applicable to clinical settings.

Objective

Exploring the value of routinely collected clinical data for phenotype classification and risk assessment of childhood asthma.

Methods

Using hospital and laboratory data, 29,851 children in a Danish nationwide database aged 2–17 years with ICS-treated asthma in 2015 followed for two years (730 days) were classified to have T2 (elevated blood eosinophils (>300 cells/μL) and/or elevated total- or specific-IgE), and/or non-T2 risk factors (in utero tobacco exposure and/or severe viral infections). Logistic regression was applied to quantify associations of risk factors with asthma severity, control, and exacerbation risk.

Results

In a complete case analysis, 85.8 % children had at least one T2 risk factor and 29.3 % had mixed T2/non-T2 risk factors. Elevated blood eosinophils and total/specific IgE were associated with exacerbations (ORs 1.55 (1.38–1.73) and 1.41 (1.20–1.66) and higher asthma severity (1.42 (1.24–1.63) and 1.31 (1.08–1.60)), respectively.

Dose-dependency was observed between blood eosinophil counts, total IgE levels, and risk of adverse outcomes. Furthermore, accumulation of risk factors demonstrated an increasing risk, with children with all four risk factors having a high risk of any adverse asthma-related outcome (OR 3.13 (2.03–4.82)

Conclusion

Asthma phenotypic markers defined in research protocols can be reliably applied in real-world settings by utilizing data collected during routine clinical care and enable better classification of risk of adverse asthma outcomes.

Background

Tuberculosis frequently poses diagnostic challenge when it presents as a peripheral pulmonary lesion (TB-PPL). The growing use of radial endobronchial ultrasound (rEBUS) for PPL biopsy highlights the need to identify predictive factors for TB-PPL, which is crucial for procedure safety.

Methods

A six-year retrospective review at our institution on adult patients with TB and malignant-PPL diagnosed from rEBUS procedure from October 1, 2016, to December 31, 2022. Clinical, radiological, procedural, histological and microbiological data were extracted and analysed.

Results

387 PPLs were included in our cohort, 32 % were TB-PPL and 68 % were malignant-PPL. The median age was 63 (IQR 55–70) years, with the TB-PPL group significantly younger. The median size of the target lesion was 2.90 (IQR 2.26–4.00) cm. The overall rEBUS diagnostic yield was 85.3 %, with a 1.3 % pneumothorax risk. Multivariate analysis identified independent predictors for TB-PPL, including age <60 years (adj OR 2.635), target lesion size <2 cm (adj OR 2.385), upper lobe location (adj OR 2.020), presence of a cavity on pre-procedural CT (adj OR 4.186), and presence of rEBUS bronchogram (adj OR 2.722). These variables achieved an area under the curve of 0.729 (95 % CI 0.673–0.795) with a diagnostic accuracy of 75.49 % (95 % CI 70.68–79.88).

Conclusions

Despite non-specific radiological findings in TB-PPL, our study identifies younger age, target lesion size less than 2 cm, upper lobe location, the presence of cavitation, and rEBUS bronchogram were independent clinical predictors for TB-PPL. This prediction model potentially helps mitigate the risk of accidental TB exposure during bronchoscopic procedures. A future prospective cohort study to validate these findings is essential to allow proper triaging of patient planning for rEBUS procedure.

Background

Tuberculosis (TB) infection screening of high-risk groups is an important strategy for achieving End TB targets. A TB infection screening program was implemented for quarry workers from a Portuguese high-incidence area in 2018–2022. We aimed to calculate the cost-benefit of the screening program from the societal perspective.

Methods

We calculated medical and non-medical direct and indirect screening costs and compared them with the cost savings from averted cases of TB disease. We estimated the number of potentially averted TB disease cases based on the risk of progression of TB infection to TB disease found in the literature.

Results

During the screening program, 997 workers were screened. TB infection was diagnosed in 215 workers, 150 of those initiated preventive treatment. Screening program total costs were €136,295. Twenty-nine TB cases were potentially prevented, what would have costed €152,386. Savings of €16,091 were obtained (€4516, €40898, and -€29322 from the workers, employers, and NHS, respectively).

Conclusions

The monetary benefit of a TB infection screening program directed to quarry workers in a high-incidence area was greater than its cost. Companies and workers saved substantially more money. TB infection tests that are better predictors of progression to TB disease could reduce NHS costs.

Background and objective

Lung function abnormality of obstructive sleep apnea (OSA) has not been explored well. Preserved ratio impaired spirometry (PRISm) is known for its association with obesity and cardiovascular morbidity, which are also characteristic features of OSA. This study aims to investigate whether the prevalence of PRISm increases according to apnea–hypopnea index levels among subjects with OSA.

Methods

Conducted as an observational cross-sectional study, the study included 372 patients ≥40 years of age with definitive diagnoses of OSA and pulmonary function assessment from 2000 to 2004. Study subjects were classified based on OSA severity (mild/moderate versus severe). The prevalence of PRISm was estimated and compared between mild/moderate and severe OSA groups.

Results

The prevalence of PRISm was 9.4 % in study subjects, with a higher prevalence in the severe OSA group than the mild/moderate group (12.9 % and 6.2 %, respectively, P = 0.04). The positive association between severe OSA and PRISm remained robust after multivariable adjustment for age, gender, and obesity (multivariable-adjusted odds ratio 2.29 (95 % confidence intervals 1.08–4.86), P = 0.03).

Conclusion

Severe OSA is an independent risk factor for PRISm, highlighting the need for comprehensive management of OSA that addresses the potential risk of PRISm.

Background

The underlying population of patients selected for each respiratory monoclonal antibody might change as other biologics are approved.

Objective

To evaluate effect modification by calendar time of the effectiveness of each respiratory biologics in asthma.

Methods

The Effectiveness of Respiratory biologics in Asthma (ERA) is a retrospective cohort of severe asthma patients from the Mass General Brigham clinics between January 2013 and September 2023. Periods were pre-specified as the anti-IgE (2013–2015), anti-IL5 (2016–2018), anti-IL4/13 (2019–2021) or anti-alarmin (2022–2023) era. We evaluated each biologic's effect on asthma-related exacerbations comparing the one-year period before and after therapy initiation using Poisson regression and Cox regression for time-to-first exacerbation.

Results

Of 647 biologic-naïve patients, 165 initiated omalizumab, 235 anti-IL5, 227 dupilumab, and 20 tezepelumab. Omalizumab's effectiveness improved as more biologics were approved: incidence rate ratio (IRR) 1.16 [0.94–1.43] anti-IgE era vs. 0.54 [0.37–0.80] anti-IL4/13-alarmin era. Omalizumab patients in the anti-IL4/13-alarmin era had lower blood eosinophil counts and less chronic rhinosinusitis with nasal polyps (CRSwNP). For anti-IL5s, effectiveness peaked in the anti-IL4/13 era (IRR 0.52 [0.42–0.64]) when patients had higher BMI and less concomitant CRSwNP. Dupilumab was most effective in the anti-IL4/13 era (IRR 0.60 [0.50–0.72]). There were fewer current smokers in dupilumab patients in the anti-IL4/13 era. Results were similar in time-to-event analyses and in sensitivity analyses accounting for the COVID-19 pandemic.

Conclusion

There are temporal variations in the effectiveness of biologics partly explained by the shift in the underlying population, particularly for omalizumab. Though having more choices was associated with better patient selection for omalizumab, this was inconsistent for other biologics.

Background

There is a lack of data on the long-term effect of nintedanib on survival in specific groups of idiopathic pulmonary fibrosis (IPF) patients with different phenotypes. We investigated the outcomes of nintedanib therapy in an observational study of a large multicentre real-world cohort of IPF patients with various initial characteristics.

Methods

The analysis included IPF patients treated with nintedanib (NIN) and IPF patients not receiving antifibrotic treatment (NAF) enrolled for the EMPIRE registry in 2015–2020. The patients were stratified according to their initial FVC predicted, dyspnoea, UIP pattern and age. All-cause mortality and annual rate of FVC decline were the main endpoints. Cox proportional hazards model for survival assessment and linear mixed-effects model for FVC decline modelling were used.

Results

A total of 869 NIN patients and 691 NAF patients were eligible for the analysis. The annual FVC decline rate was significantly different (adjusted values −0.053 l/yr vs −0.122 l/yr; p = 0.001). The adjusted hazard ratio (HR) for mortality was 0.40 (95 % CI 0.3 to 0.53, p < 0.001). The most significant effect of nintedanib was demonstrated in patients with impaired lung function, i.e., with an FVC predicted to be less than 80 % and a NYHA II to IV. Nintedanib therapy also reduced the difference in survival between men and women.

Conclusions

Modelling confirmed that NIN therapy reduced differences in OS between patients with better and worse initial conditions and prognosis. Our results indicate that NIN is particularly beneficial for patients with advanced IPF and more severe phenotypes.

Trial registration

EMPIRE was registered as a non-interventional post-registration study at the State Institute for Drug Control of the Czech Republic under ID 1412080000 on December 8, 2014.

Objective

This study aimed to develop and validate a nomogram for predicting 28-day and 90-day mortality in intensive care unit (ICU) patients who have chronic obstructive pulmonary disease (COPD) coexisting with congestive heart failure (CHF).

Methods

An extensive analysis was conducted on clinical data from the Medical Information Mart for Intensive Care IV database, covering patients over 18 years old with both COPD and CHF, who were were first-time ICU admissions between 2008 and 2019. The least absolute shrinkage and selection operator (LASSO) regression method was employed to screen clinical features, with the final model being optimized using backward stepwise regression guided by the Akaike Information Criterion (AIC) to construct the nomogram. The predictive model's discrimination and clinical applicability were evaluated via receiver operating characteristic (ROC) curves, calibration curves, the C-index, and decision curve analysi s (DCA).

Results

This analysis was comprised of a total of 1948 patients. Patients were separated into developing and validation cohorts in a 7:3 ratio, with similar baseline characteristics between the two groups. The ICU mortality rates for the developing and verification cohorts were 20.8 % and 19.5 % at 28 days, respectively, and 29.4 % and 28.3 % at 90 days, respectively. The clinical characteristics retained by the backward stepwise regression include age, weight, systolic blood pressure (SBP), respiratory rate (RR), oxygen saturation (SpO2), red blood cell distribution width (RDW), lactate, partial thrombosis time (PTT), race, marital status, type 2 diabetes mellitus (T2DM), malignant cancer, acute kidney failure (AKF), pneumonia, immunosuppressive drugs, antiplatelet agents, vasoactive agents, acute physiology score III (APS III), Oxford acute severity of illness score (OASIS), and Charlson comorbidity index (CCI). We developed two separate models by assigning weighted scores to each independent risk factor: nomogram A excludes CCI but includes age, T2DM, and malignant cancer, while nomogram B includes only CCI, without age, T2DM, and malignant cancer. Based on the results of the AUC and C-index, this study selected nomogram A, which demonstrated better predictive performance, for subsequent validation. The calibration curve, C-index, and DCA results indicate that nomogram A has good accuracy in predicting short-term mortality and demonstrates better discriminative ability than commonly used clinical scoring systems, making it more suitable for clinical application.

Conclusion

The nomogram developed in this study offers an effective assessment of short-term mortality risk for ICU patients with COPD and CHF, proving to be a superior tool for predicting their short-term prognosis.

Background

Dyspnea is an important non-motor symptom in Parkinson's disease (PD) that impacts quality of life. The mechanisms underlying dyspnea have been difficult to determine due to challenges separating central respiratory control abnormalities from peripheral respiratory muscle dysfunction and chest wall rigidity.

Methods

A comprehensive literature review was conducted, searching the PubMed database for observational studies on respiratory dysfunction and dyspnea in PD. Inclusion criteria were studies with PD patients without other neurological disorders. Case studies were excluded. Data on study size, disease duration, control groups, and respiratory defects were extracted.

Results

The search yielded 23 unique publications on pulmonary function in PD. Key findings were: 1) restrictive defects are common, with prevalence up to 85 % in some studies; 2) effects of levodopa on pulmonary function are variable across studies; 3) there is limited research on the role of central respiratory centers in dyspnea pathophysiology in PD. Proposed mechanisms include direct involvement of brainstem respiratory structures, loss of dopamine input to these regions, and astrocyte dysfunction affecting respiratory rhythm generation.

Conclusion

This review outlines potential mechanisms underlying dyspnea in PD, including central respiratory dysfunction, peripheral muscle/chest wall abnormalities, impaired respiratory sensation, and medication effects. More research is needed investigating specific brainstem regions involved, chemoreceptor pathology, correlations between respiratory load and perceived dyspnea, and medication effects on pulmonary function.

Background

Poor glucose control might deteriorate the impaired pulmonary function, which can ultimately lead to mortality. However, few studies have examined the effect modification of glucose control on the association between pulmonary function and mortality. This study aimed to examine the association of pulmonary function with mortality and determine the effect modification of glycemic level on the association of pulmonary function with mortality in persons with type 2 diabetes (T2DM).

Methods

A retrospective cohort study included 3846 persons with T2DM with pulmonary function testing in Taiwan during 2002–2020. Expiratory volume in 1 s (FEV1) was measured as pulmonary function. Cox proportional hazards models were used and the effect modification of pulmonary function parameters and glucose control was assessed by their product terms.

Results

There were 733 deaths during an average follow-up of 7.83 years. Significant associations of FEV1 and mortality were found (hazards ratio [HR] for FEV1 Z-scores of <0 to −1, <-1 to −2 and <−2: 1.47 [1.20, 1.80], 2.48 [1.95, 3.14] and 3.07 [1.74, 5.44] compared with participants with Z-score ≥0, respectively. All p for trend<0.001). Significant effect modifications were found and the association between FEV1 and mortality was stronger in persons with good glycemic control compared with poor glycemic control (FEV1–FPG effect modification, P = 0.01; FEV1–HbA1c effect modification, P = 0.03).

Conclusion

Pulmonary function, measured by FEV1, is significantly associated with mortality in persons with T2DM. Significant effect modification of glucose control on the association between pulmonary function parameters and mortality was found.

Background

Whether the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV₁/FVC) can be used as a biomarker to predict the risk of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is unclear.

Methods

To investigate the predictive role of FEV₁/FVC for AECOPD, we analyzed data from an observational and multicenter cohort study of 2043 patients with COPD in KOREA. Exposures were post-bronchodilator FEV₁/FVC and/or percentage predicted FEV₁ (FEV₁%pred). The outcome was the development of AECOPD during the first year of follow-up.

Results

During the first year of follow-up, the proportion of patients who developed AECOPD increased as FEV₁/FVC decreased (P < 0.01). FEV₁/FVC and FEV₁%pred had similar predictive power for AECOPD, with optimal predictive cut-offs of approximately 0.5 for FEV₁/FVC and 50 % for FEV₁%pred. When the participants were classified into groups based on these cut-offs, compared with a high both-lung function group (FEV₁/FVC≥0.5 and FEV₁%pred≥50 %), the low-FEV₁ group (FEV₁/FVC≥0.5 and FEV₁%pred<50) had a modestly increased risk of severe AECOPD (adjusted odds ratio[aOR] = 3.12; 95 % confidence interval[CI] = 1.59–6.16), while the risk of severe AECOPD was the highest in the low both-lung function group (FEV₁%pred<50 % and FEV₁/FVC<0.5) (aOR = 5.16; 95 % CI = 3.34–7.97).

Conclusions

FEV₁/FVC is a spirometric biomarker predictive of AECOPD. In countries where FEV₁%pred is not available for their population, FEV₁/FVC could be used as a biomarker for assessing the risk of AECOPD. In countries where accurate FEV₁%pred is available, both FEV₁%pred and FEV₁/FVC could be used to provide additional information to assess the risk of AECOPD.

Key message

This study showed that FEV₁/FVC had similar predictive power for AECOPD compared with percentage predicted FEV₁. Furthermore, the use of both FEV₁ and FEV₁/FVC provides additional information for the risk assessment of AECOPD.