Use of FEV1 in cystic fibrosis epidemiologic studies and clinical trials: A statistical perspective for the clinical researcher

Background

Forced expiratory volume in 1 s (FEV₁) is an established marker of cystic fibrosis (CF) disease progression that is used to capture clinical course and evaluate therapeutic efficacy. The research community has established FEV₁ surveillance data through a variety of observational data sources such as patient registries, and there is a growing pipeline of new CF therapies demonstrated to be efficacious in clinical trials by establishing improvements in FEV₁.

Assessment of Immune-Related Interstitial Lung Disease in Patients With NSCLC Treated with Immune Checkpoint Inhibitors: A Multicenter Prospective Study

IntroductionProgrammed cell death protein 1 immune checkpoint inhibitors (ICIs) have been reported to improve the survival of patients with NSCLC. On the expansion of clinical administration for a variety of cancers, immune-related adverse events have been typically recognized to be associated with ICIs, therefore, necessitating the monitoring and management of these patients. Among immune-related adverse events, immune-related interstitial lung disease (ir-ILD) is a serious complication that interrupts treatment and can occasionally be fatal. However, no prospective studies have investigated the incidence of ir-ILD and associated risk factors for its development in the clinical setting.MethodsThis is a prospective cohort study consisting of patients with NSCLC treated with ICIs. Baseline characteristics, including laboratory data, pulmonary function tests, daily symptoms of dyspnea defined by the modified Medical Research Council, and antitumor response were assessed.ResultsAmong the 138 patients with NSCLC who received anti–programmed cell death protein 1 monotherapy, 20 patients (14.5%) had ir-ILD within median 51.5 days (interquartile range: 29–147). This was approximately three times higher than those in clinical trials. A total of 11 patients (55.0%), including all eight patients with high-grade ir-ILD (≥grade 3), developed ir-ILD within 60 days. Impaired spirometry, decreased forced vital capacity and forced expiratory volume in 1 second, and daily symptoms of dyspnea measured using the modified Medical Research Council scale were identified as risk factors for ir-ILD development. In addition, combination assessment of forced vital capacity and forced expiratory volume in 1 second successfully classified patients at risk for ir-ILD development.ConclusionsThe incidence of ir-ILD was substantially higher in the clinical setting. Assessment of spirometry and daily dyspneic symptoms before ICI treatment may be useful in monitoring and managing patients with NSCLC.     

硫酸镁对重度支气管哮喘患儿肺功能的影响

目的观察硫酸镁对重度支气管哮喘患儿肺功能的影响。方法重度支气管哮喘患儿42例,随机分为两组。治疗组在常规治疗基础上,辅以25mg／kg硫酸镁溶液静脉滴注和60mg／ml硫酸镁溶液2．5ml雾化吸入。对照组予地塞米松等效量静脉滴注0．75mg／（kg·d）,2次／d;3d后监测哮喘缓解情况,哮鸣音消失时间、最大呼气峰流速（PEFR）、第1秒最大呼气率（FEV1％）、用力肺活量（FVC）、血气分析、血镁、尿镁等指标的变化。结果治疗组在哮喘缓解时间,哮鸣音消失时间,PaO2、PH、PEFR、FEV1％与对照组间差异有显著性。镁剂造成的不良反应轻微,两组药物反应发生率差异无统计学意义。结论硫酸镁对重度支气管哮喘的症状和肺功能有明显改善。     

Improvement of Pulmonary Functions Following Septoplasty: How Are Lower Airways Affected?

ObjectivesNasal septal deviation is a frequent cause of increased nasal airway resistance. A narrow nasal airway would result in a decreased airflow into the lungs. The aim of the present study was to evaluate the alterations of the pulmonary functions following septoplasty using spirometry and 6 minutes walking test (6mWT). And reveal the correlation of symptom score improvement with nasal obstruction symptom score (NOSE) and sino-nasal outcome test (SNOT22) questionnaires following surgery.MethodsThirty patients with obvious nasal septal deviations were enrolled in the study. All patients had a detailed otorhinolaryngologic examination, filled NOSE/SNOT22 questionnaires, performed spirometry and 6mWT preoperatively. One month after surgery, NOSE/SNOT22 questionnaires filled by subjects and spirometry with 6mWT were performed again, and the results were compared.ResultsThe mean total walking distance was 702.3±68.2 m preoperatively, and it improved to 753.2±72.6 m postoperatively (P<0.001). Total tour count increased from 11 (range, 10.8 to 12.0) to 12 (range, 11 to 13.3), and the difference was found statistically significant (P<0.001). When the preoperative and postoperative mean 6mWT results were compared, diastolic blood pressure increased from 70 to 80 mmHg (P=0.031), heart rate increased from 83.5±13.2 to 90.1±12.5 bpm (P=0.017), dyspnea rate decreased from 1 to 0 (P=0.002), and fatigue scores reduced from 2 to 1 (P=0.003). Evaluation on spirometry findings revealed that FIF_50% (maximum inspiratory flow at 50% of forced vital capacity [FVC]) scores and peak expiratory flow (PEF) values improved significantly after surgery. Septoplasty improves the nasal breathing pattern. While reducing FEF_50% (maximum expiratory flow at 50% of FVC)/FIF_50%, it increases PEF and FIF_50% values. In addition, as shown by 6mWT, exercise capacity improves following surgery. Postoperative NOSE and SNOT22 scores reduced markedly compared to preoperative values (P<0.001).ConclusionThese findings suggest that nasal septal surgery has a positive effect on pulmonary functions, and this can be an important clue for the relationship of lung disorders and nasal obstruction.     

Small airway disease and its predictors in patients with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a connective tissue disease, characterized by symmetric peripheral polyarthritis. Extra-articular disease occurs in approximately 50% of the patients with lung being a common site. The presence of functional or morphological abnormalities in small airways has recently been noted in patients with RA but its exact prevalence and clinical significance is still a subject of debate. This study was aimed to determine the prevalence of small airway disease (SAD) in patients with RA and the factors influencing it.MethodsFifty consecutive patients with RA were included in this cross-sectional observational study. All patients were subjected to pulmonary function tests (PFT) including Spirometry and Forced Oscillation technique (FOT). Those with features of SAD on PFT were subjected to High-Resolution Computed Tomography (HRCT) of the chest.ResultsSpirometry was suggestive of SAD in 17 patients, with 34% prevalence and FOT was abnormal in 9 patients, with 18% prevalence in the study population. Of 17 patients with SAD on spirometry, 8 (47.05%) patients showed mosaic attenuation, a sign of SAD on the HRCT chest. On univariate analysis, age, Disease Activity Score (DAS-28), joint erosions on X-ray, RF and anti-CCP were found to be associated with SAD.ConclusionSAD was present in one-third of the patients with RA, even in those with short duration of disease, low to moderate disease activity and no respiratory symptoms. It is thus inferred that the complete workup of RA patients should include pulmonary function assessment.     

Restrictive pattern on spirometry: association with cardiovascular risk and level of physical activity in asymptomatic adults

Objective

: To determine whether a restrictive pattern on spirometry is associated with the level of physical activity in daily life (PADL), as well as with cardiovascular disease (CVD) risk factors, in asymptomatic adults.

Methods

: A total of 374 participants (mean age, 41 ± 14 years) underwent spirometry, which included the determination of FVC and FEV₁. A restrictive pattern on spirometry was defined as an FEV₁/FVC ratio > 0.7 and an FVC < 80% of the predicted value. After conducting demographic, anthropometric, and CVD risk assessments, we evaluated body composition, muscle function, and postural balance, as well as performing cardiopulmonary exercise testing and administering the six-minute walk test. The PADL was quantified with a triaxial accelerometer.

Results

: A restrictive pattern on spirometry was found in 10% of the subjects. After multivariate logistic regression, adjusted for confounders (PADL and cardiorespiratory fitness), the following variables retained significance (OR; 95% CI) as predictors of a restrictive pattern: systemic arterial hypertension (17.5; 1.65-184.8), smoking (11.6; 1.56-87.5), physical inactivity (8.1; 1.43-46.4), larger center-of-pressure area while standing on a force platform (1.34; 1.05-1.71); and dyslipidemia (1.89; 1.12-1.98).

Conclusions

: A restrictive pattern on spirometry appears to be common in asymptomatic adults. We found that CVD risk factors, especially systemic arterial hypertension, smoking, and physical inactivity, were directly associated with a restrictive pattern, even when the analysis was adjusted for PADL and cardiorespiratory fitness. Longitudinal studies are needed in order to improve understanding of the etiology of a restrictive pattern as well as to aid in the design of preventive strategies.     

Changes in the Flow-Volume Curve According to the Degree of Stenosis in Patients With Unilateral Main Bronchial Stenosis

Objectives

The shape of the flow-volume (F-V) curve is known to change to showing a prominent plateau as stenosis progresses in patients with tracheal stenosis. However, no study has evaluated changes in the F-V curve according to the degree of bronchial stenosis in patients with unilateral main bronchial stenosis.

Methods

We performed an analysis of F-V curves in 29 patients with unilateral bronchial stenosis with the aid of a graphic digitizer between January 2005 and December 2011.

Results

The primary diseases causing unilateral main bronchial stenosis were endobronchial tuberculosis (86%), followed by benign bronchial tumor (10%), and carcinoid (3%). All unilateral main bronchial stenoses were classified into one of five grades (I, ≤25%; II, 26%-50%; III, 51%-75%; IV, 76%-90%; V, >90% to near-complete obstruction without ipsilateral lung collapse). A monophasic F-V curve was observed in patients with grade I stenosis and biphasic curves were observed for grade II-IV stenosis. Both monophasic (81%) and biphasic shapes (18%) were observed in grade V stenosis. After standardization of the biphasic shape of the F-V curve, the breakpoints of the biphasic curve moved in the direction of high volume (x-axis) and low flow (y-axis) according to the progression of stenosis.

Conclusion

In unilateral bronchial stenosis, a biphasic F-V curve appeared when bronchial stenosis was >25% and disappeared when obstruction was near complete. In addition, the breakpoint moved in the direction of high volume and low flow with the progression of stenosis.