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Background: Posttraumatic stress disorder (PTSD) symptomatology and poorer pulmonary function are highly prevalent psychiatric and medical conditions. In the present study, we tested for the individual, additive, and modifying associations of PTSD symptomatology and pulmonary function with cognitive performance. Methods: In this cross‐sectional study, a total of 1,401 World Trade Center (WTC) responders (mean age = 53, SD = 8 years, 92% males) participated in the study. Cogstate assessment measured cognitive performance. PTSD symptomatology was measured using the trauma‐specific version of the posttraumatic stress disorder checklist (PCL‐17) adapted for the WTC attacks. The 1‐second forced expiratory volume and forced vital capacity (FEV1/FVC) ratio was used to measure pulmonary function. Linear regressions with cognitive performance as the outcome were conducted to assess individual, additive, and moderating associations of PTSD symptomatology and pulmonary function. Results: Higher PTSD symptomatology and poorer pulmonary function were negatively associated with cognitive performance. A 10% increase on the FEV1/FVC ratio moderated the association between PTSD symptomatology and cognition, whereby its association with cognition was stronger when PTSD symptomatology was higher (est. = 0.01, 95%CI = 0.004, 0.01, p < 0.001). When stratified by responder type, these associations persisted in trained (est. = 0.01, 95%CI = 0.01, 0.02, p < 0.001), but not in non‐trained (est. = 0.004, 95% C.I. = −0.01, 0.02, p = 0.39) responders. Conclusions: In the presence of higher PTSD, better pulmonary functioning is associated with better cognitive performance. Early intervention efforts to mitigate preventable cognitive decline in high‐risk populations should be studied, especially since intervention in one modality may have an impact on others. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Evaluations of pulmonary, cough, and swallow function are frequently performed to assess disease progression in amyotrophic lateral sclerosis (ALS), yet the relationship between these functions remains unknown. We therefore aimed to determine relationships between these measures in individuals with ALS. Methods: One hundred individuals with ALS underwent standardized tests: forced vital capacity (FVC), maximum expiratory/inspiratory pressure (MEP, MIP), voluntary cough peak expiratory flow (PEF), and videofluoroscopic swallow evaluation (VF). Duplicate raters completed independent, blinded ratings using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale. Descriptives, Spearman's Rho correlations, Kruskal–Wallis analyses, and Pearson's chi‐squared tests were completed. Results: Mean and standard deviation across pulmonary and cough measures were FVC: 74.2% predicted (± 22.6), MEP: 91.6 cmH2O (± 46.4), MIP cmH2O: 61.1 (± 28.9), voluntary PEF: 352.7 L/min (± 141.6). DIGEST grades included: 0 (normal swallowing): 31%, 1 (mild dysphagia): 48%, 2 (moderate dysphagia): 10%, 3 (severe dysphagia): 10%, and 4 (life‐threatening dysphagia): 1%. Positive correlations were observed: MEP‐MIP: r =.76, MIP‐PEF: r =.68, MEP‐PEF: r =.61, MIP‐FVC: r =.60, PEF‐FVC: r =.49, and MEP‐FVC: r =.46, p <.0001. MEP (p =.009) and PEF (p =.04) differed across DIGEST safety grades. Post hoc analyses revealed significant between group differences in MEP and PEF across DIGEST safety grades 0 versus 1 and grades 0 versus 3, (p <.05). Discussion: In this cohort of individuals with ALS, pulmonary function, and voluntary cough were associated. Expiratory metrics (MEP, PEF) were diminished in individuals with unsafe swallowing, increasing their risk for effectively defending the airway. [ABSTRACT FROM AUTHOR]

Prognosticating acute lung injury (ALI) is challenging, in part because of a lack of sensitive biomarkers. Hyperpolarized gas magnetic resonance (MR) has unique advantages in pulmonary function measurement and can provide promising biomarkers for the assessment of lung injuries. Herein, we employ hyperpolarized 129Xe MRI and generate a number of imaging biomarkers to detect the pulmonary physiological and morphological changes during the progression of ALI in an animal model. We find the measured ratio of 129Xe in red blood cells to interstitial tissue/plasma (RBC/TP) is significantly lower in the ALI group on the second (0.32 ± 0.03, p = 0.004), seventh (0.23 ± 0.03, p < 0.001), and 14th (0.29 ± 0.04, p = 0.001) day after lipopolysaccharide treatment compared with that in the control group (0.41 ± 0.04). In addition, significant differences are also observed for RBC/TP measurements between the second and seventh day (p = 0.001) and between the seventh and 14th day (p = 0.018) in the ALI group after treatment. Besides RBC/TP, significant differences are also observed in the measured exchange time constant (T) on the second (p = 0.038) and seventh day (p = 0.009) and in the measured apparent diffusion coefficient (ADC) and alveolar surface‐to‐volume ratio (SVR) on the 14th day (ADC: p = 0.009 and SVR: p = 0.019) after treatment in the ALI group compared with that in the control group. These findings indicate that the parameters measured with 129Xe MR can detect the dynamic changes in pulmonary structure and function in an ALI animal model. [ABSTRACT FROM AUTHOR]

Organ dysfunction, including pulmonary function impairment, plays a key role in the choice of conditioning chemotherapy before autologous hematopoietic stem cell transplantation (auto‐HSCT). Replacement of BCNU/carmustine as part of BEAM (BCNU/carmustine, etoposide, cytarabine, and melphalan) conditioning protocol by thiotepa (TEAM) reduces pulmonary toxicity while maintaining efficacy. We retrospectively analyzed the association of clinical characteristics, comorbidities, and organ function with outcomes after conditioning with BEAM or TEAM. Three hundred ninety‐six patients undergoing auto‐HSCT (n = 333 with BEAM; n = 63 with TEAM) at our institution between 2008 and 2021 were included in this study. In the multivariate analysis, CO‐diffusion capacity corrected for hemoglobin (DLCOcSB) ≤ 60% of predicted, progressive disease (PD) before auto‐HSCT, Karnofsky performance score (KPS) ≤ 80%, HCT‐CI score ≥ 4, and cardiac disease before auto‐HSCT were associated with decreased overall survival (OS) in patients treated with BEAM. In contrast, only PD before auto‐HSCT was identified in patients treated with TEAM. Patients conditioned with BEAM and DLCOcSB ≤ 60% had higher non‐relapse mortality, including pulmonary cause of death. In summary, we have identified clinical and pulmonary risk factors associated with worse outcomes in patients conditioned with BEAM compared to TEAM. Our data suggest TEAM conditioning as a valid alternative for patients with comorbidities, including pulmonary dysfunction and/or poorer performance scores, before auto‐HSCT. [ABSTRACT FROM AUTHOR]

Objectives: To examine the feasibility of individuals with spinal cord injury or disease (SCI/D) to perform combined oropharyngeal and respiratory muscle training (RMT) and determine its impact on their respiratory function. Methods: A prospective study at a single Veterans Affairs (VA) Medical Center. Inclusion criteria included: 1) Veterans with chronic SCI/D (>6 months postinjury and American Spinal Injury Association (ASIA) classification A–D) and 2) evidence of OSA by apnea‐hypopnea index (AHI ≥5 events/h). Eligible participants were randomly assigned to either an experimental (exercise) group that involved performing daily inspiratory, expiratory (using POWERbreathe and Expiratory Muscle Strength Trainer 150 devices, respectively), and tongue strengthening exercises or a control (sham) group that involved using a sham device, for a 3‐month period. Spirometry, maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP), polysomnography, and sleep questionnaires were assessed at baseline and at 3 months. Results: Twenty‐four individuals were randomized (12 participants in each arm). A total of eight (67%) participants completed the exercise arm, and ten (83%) participants completed the sham arm. MIP was significantly increased (p < 0.05) in the exercise group compared with the baseline. Conclusions: Combined oropharyngeal and RMT are feasible for individuals with SCI/D. Future studies are needed to determine the clinical efficacy of these respiratory muscle exercises. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between periodontitis and lung function in the Malmö Offspring Dental Study. Materials and Methods: In all 1001 individuals (49.9% female, mean age: 44.6) from Malmö Offspring Dental Study were included. Periodontitis was assessed by a full‐mouth examination protocol including bleeding on probing and classified according to the American Academy of Periodontology/Center for Disease Control definitions. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were expressed as absolute values and %predicted according to Global Lung Function Initiative reference values. FEV1, FVC and FEV1/FVC were analysed in relation to periodontal status using linear regression. Results: Severe periodontitis was found in 7% of the population. Adjusted regression models showed significant associations between lung function and severe periodontitis with 2.1 unit lower FEV1/FVC ratio (95% CI: −3.91, –0.23) and odds ratio (adjusted) of 2.56 (95% CI: 1.40, 4.75, p =.003) for airflow obstruction (FEV1/FVC less than the lower limit of normal) if having severe periodontitis. Lower values of %predicted FEV1 and %predicted FVC, but not FEV1/FVC, were found in individuals with >25% bleeding on probing. Conclusions: Severe periodontitis was associated with lower FEV1/FVC ratio and airflow obstruction in the present cohort. More large‐scale prospective studies and intervention studies are required for a comprehensive evaluation. [ABSTRACT FROM AUTHOR]

Background and Objective: This study aimed to evaluate the longitudinal changes in cardiopulmonary function (CPF) and identify predictors of cardiopulmonary recovery failure after lung cancer surgery. Methods: Data was obtained from a prospective CATCH‐LUNG cohort study, where patients were divided into two groups based on 6‐min walk distance (6MWD) at baseline and 6 months after surgery. CPF recovery failure was defined as a participant whose 6MWD dropped over 50 m from baseline to 6 months after surgery. Patients with a baseline 6MWD less than 400 m were excluded. The analysis was investigated using mixed effects models, and the relative estimates for the predictors were expressed relative risk (RR) and 95% CI using a Poisson regression. Results: Among 419 patients, 24.1% and 17.7% showed failure of CPF recovery at 6 months and 1 year after surgery, respectively. In the multivariable analysis, baseline step count [RR per 1000 steps lower = 1.05 (95% CI, 1.01–1.09)], baseline dyspnoea [RR per 10 points higher = 1.15(1.07–1.23)], decreased FEV1% predicted from baseline to 2 weeks after surgery [RR per 10% lower = 1.30(1.10–1.53)] and decreased moderate‐to‐vigorous physical activity (MVPA) from baseline to 2 weeks [RR = 1.95(1.22, 3.11)] or persistent low MVPA at baseline and 2 weeks after surgery [RR = 1.63(1.04, 2.54)] were significant factors for loss of CPF. Conclusion: The inability to recover CPF at 6 months after surgery was linked to reduction of lung function and MVPA from baseline to 2 weeks as well as baseline physical activity (PA) and dyspnoea. These results imply that engagement of perioperative PA is necessary to facilitate recovery of CPF after lung cancer surgery. [ABSTRACT FROM AUTHOR]

Objective: A deviated nasal septum (DNS) can result in an anatomical obstruction and impact lung function through prolonged suboptimal inspiration. Given the improvements in respiration reported by patients following septoplasty or septorhinoplasty (with or without inferior turbinate reduction), our study investigated the effect of these procedures on pulmonary function through a systematic review and meta‐analysis. Data Sources: Medline, Embase, Cochrane Databases, Web of Science, and Google Scholar. Review Methods: The review was registered with PROSPERO [CRD42022316309]. The study population was composed of adult patients (18–65) who were symptomatic with confirmed DNS. Extracted outcomes (pre‐operative versus postoperative) included the six‐minute walk test (6MWT) and pulmonary function tests (FEV1, FVC, FEV1/FVC, FEF25‐75, PEF). Meta‐analyses were performed using a random‐effects model. Results: Three studies included measures of the 6MWT in meters and all three found a statistically significant increase in the distance walked after surgery with a mean difference of 62.40 m (95% CI 24.79–100.00). Statistically significant improvements in PFT outcomes were observed with a standard mean difference of 0.72 for FEV1 (95% CI 0.31–1.13), 0.63 for FVC (95% CI 0.26–1.00), and 0.64 for PEF (95% CI 0.47–0.82). Of the twelve studies which measured PFT outcomes, six showed statistically significant improvements, three studies showed mixed results, and three studies found no difference in PFT outcomes between pre‐and post‐surgery testing. Conclusions: The present study suggests that pulmonary function does improve after nasal surgery for DNS, but the high heterogeneity observed in the meta‐analyses indicates that the evidence supporting this conclusion is low. Laryngoscope, 133:2837–2845, 2023 [ABSTRACT FROM AUTHOR]

Aims: Type 1 diabetes is associated with a substantially increased risk of impaired lung function, which may impair aerobic fitness. We therefore aimed to examine the ventilatory response during maximal exercise and the pulmonary diffusion capacity function at rest in individuals with uncomplicated type 1 diabetes. Methods: In all, 17 adults with type 1 diabetes free from micro–macrovascular complications (glycated haemoglobin: 8.0 ± 1.3%), and 17 non‐diabetic adults, carefully matched to the type 1 diabetes group according to gender, age, level of physical activity and body composition, participated in our study. Lung function was assessed by spirometry and measurements of the combined diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) at rest. Subjects performed a maximal exercise test during which the respiratory parameters were measured. Results: At rest, DLCO (30.4 ± 6.1 ml min−1 mmHg−1 vs. 31.4 ± 5.7 ml min−1 mmHg−1, respectively, p = 0.2), its determinants Dm (membrane diffusion capacity) and Vc (pulmonary capillary volume) were comparable among type 1 diabetes and control groups, respectively. Nevertheless, spirometry parameters (forced vital capacity = 4.9 ± 1.0 L vs. 5.5 ± 1.0 L, p < 0.05; forced expiratory volume 1 = 4.0 ± 0.7 L vs. 4.3 ± 0.7 L, p < 0.05) were lower in individuals with type 1 diabetes, although in the predicted normal range. During exercise, ventilatory response to exercise was different between the two groups: tidal volume was lower in type 1 diabetes vs. individuals without diabetes (p < 0.05). Type 1 diabetes showed a reduced VO2max (34.7 ± 6.8 vs. 37.9 ± 6.3, respectively, p = 0.04) in comparison to healthy subjects. Conclusions: Individuals with uncomplicated type 1 diabetes display normal alveolar‐capillary diffusion capacity and at rest, while their forced vital capacity, tidal volumes and VO2 are reduced during maximal exercise. [ABSTRACT FROM AUTHOR]

Introduction: Overweight and obese children are at risk of obstructive sleep apnoea (OSA) and abnormal pulmonary function (PF). Aim: Investigate the relationship between body mass index (BMI), OSA on PF in children. Materials & Method: Seventy‐four children were recruited. Mixed obstructive apnoea‐hypopnea index (MOAHI), BMI, oxygen saturation (SpO2), forced expiratory volume one second (FEV1), forced vital capacity (FVC) and fractionated exhaled nitric oxide (FeNO) were measured. Results: Twenty‐four and thirty children had mild OSA and moderate‐to‐severe OSA respectively. BMI correlated negatively with SpO2 nadir (r = −.363, p =.001). FVC, FEV1 and nadir SpO2 values decreased with OSA severity (p <.001). The odds of a child with OSA having an abnormal spirometry was 3.16 (95% CI: 1.08, 9.22). There was significant association between FeNO and AHI (r =.497, <.001). Discussion: Overweight and obese children with OSA have significant abnormalities in pulmonary function independent of BMI. OSA severity and elevated FeNO also correlated with diminishing lung function. [ABSTRACT FROM AUTHOR]

Background and Objective: The optimal management of unclassifiable Interstitial lung disease (ILD) remains a challenge. The aim of this study was to describe pulmonary function trajectories for patients treated with immunomodulatory therapy and for untreated patients. Methods: Clinical information and treatment data were obtained retrospectively at two ILD centres. Pulmonary function data were analysed using (1) mixed effects linear regression models with and without clinical covariates and (2) propensity score matching using gender, age, physiology (GAP) stage, smoking and presence of ground glass opacities. Results: Sixty‐five percent of the 249 patients included received corticosteroids and/or other immunomodulators. Treated patients had lower forced vital capacity (FVC) (72% vs. 83% predicted) and diffusing capacity for carbon monoxide (DLco) (44% vs. 60% predicted). In mixed effects linear regression, the adjusted change in FVC was −0.22%, [−0.34; −0.11], and −0.15% [−0.28;‐0.012] for DLco. The difference in pulmonary function decline between treated and untreated patients was insignificant, −0.082% per month, [−0.28; 0.11], p = 0.10 for FVC and −0.14% per month, [−0.36; 0.079], p = 0.15, for DLco. In propensity score matched analysis, the difference in change in FVC was 0.039% per month, p = 0.12, and for DLco, 0.0085% per month, p = 0.7. Conclusion: The pulmonary function trajectories for treated and untreated patients were parallel, despite treated patients having more severe disease at baseline. The persisting differences between the groups suggest no overall effect, although improvement or stabilization may be seen in some patients. Prospective studies are needed to define subsets of patients with unclassifiable interstitial lung disease and their optimal management. Patients with unclassifiable interstitial lung disease who received immunomodulatory therapy had similar pulmonary function trajectories as patients who did not receive therapy despite more severe disease at baseline in treated patients. This suggests a lack of overall improvement, although immunomodulatory therapy may have effect in a subgroup of patients. [ABSTRACT FROM AUTHOR]

Background: Sleeve lobectomy is recommended to avoid pneumonectomy and preserve pulmonary function in patients with central lung cancer. However, the relationship between postoperative pulmonary functional loss and resected lung parenchyma volume has not been fully characterized. The aim of this study was to evaluate the relationship between pulmonary function and lung volume in patients undergoing sleeve lobectomy or pneumonectomy. Methods: A total of 61 lung cancer patients who had undergone pneumonectomy or sleeve lobectomy were analyzed retrospectively. Among them, 20 patients performed pulmonary function tests, including vital capacity (VC) and forced expiratory volume in 1 s (FEV1) tests, preoperatively and then about 6 months after surgery. VC and FEV1 ratios were calculated (measured postoperative respiratory function/predicted postoperative respiratory function) as the standardized pulmonary functional loss ratio. Results: Thirty‐day operation‐related mortality was significantly lower after sleeve lobectomy (3.2%) than pneumonectomy (9.6%). The 5‐year relapse‐free survival rate was 46.67% versus 29.03%, and the 5‐year overall survival rate was 63.33% versus 38.71% in patients receiving sleeve lobectomy versus pneumonectomy. The VC ratio in the pneumonectomy group was better than in the sleeve lobectomy group (1.003 ± 0.117 vs. 0.779 ± 0.12; p = 0.0008), as was the FEV1 ratio (1.132 ± 0.226 vs. 0.851 ± 0.063; p = 0.0038). Conclusions: Both short‐term and long‐term outcomes were better with sleeve lobectomy than pneumonectomy. However, actual postoperative pulmonary function after pneumonectomy may be better than clinicians expect, and pneumonectomy should still be considered a treatment option for patients with sufficient pulmonary reserve and in whom sleeve lobectomy is less likely to be curative. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of rituximab (RTX) on lung function and the prevalence of adverse events (AEs) in connective tissue disease‐associated interstitial lung disease (CTD‐ILD) by meta‐analysis. Methods: EMBASE, Web of Science, PubMed and ClinicalKey were searched up to July 16, 2021. The lung function (forced vital capacity, FVC% predicted, and diffusing capacity of the lung for carbon monoxide, DLCO% predicted) and prevalence of AEs of RTX in CTD‐ILD were analyzed by meta‐analysis, and 95% confidence interval (CI) was calculated. Subgroup analyses and meta‐regression were used to explore the heterogeneity. Results: We identified 29 studies, including 827 CTD‐ILD patients with a median age of 53.05 years. In observational studies, FVC% (mean difference − 1.24, 95% CI [−2.35, −0.12]; P =.030) and DLCO% (−7.71, [−11.79, −3.63]; P =.014) of CTD‐ILD decreased significantly after RTX treatment. In randomized controlled trials, FVC% of CTD‐ILD decreased after RTX treatment (−5.24, [−9.94, − 0.54]; P =.029), but the difference of DLCO% was not significant (1.15, [−4.33, 6.63]; P =.681). The prevalence of AEs, all‐cause mortality and infections was 29.7% (95% CI [0.17, 0.42]), 11.6% (95% CI [0.08, 0.16]) and 20.9% (95% CI [0.15, 0.27]), respectively. Conclusions: RTX was associated with AEs such as decreased pulmonary function, all‐cause mortality, and infections in CTD‐ILD. Adverse reactions during and after RTX treatment should be carefully monitored. Further prospective studies are needed to compare RTX with other immunosuppressants, antifibrotic drugs or placebos, which can provide therapeutic approaches for CTD‐ILD. [ABSTRACT FROM AUTHOR]

Background and objective: Prediction of disease course in patients with progressive pulmonary fibrosis remains challenging. The purpose of this study was to assess the prognostic value of lung fibrosis extent quantified at computed tomography (CT) using data‐driven texture analysis (DTA) in a large cohort of well‐characterized patients with idiopathic pulmonary fibrosis (IPF) enrolled in a national registry. Methods: This retrospective analysis included participants in the Australian IPF Registry with available CT between 2007 and 2016. CT scans were analysed using the DTA method to quantify the extent of lung fibrosis. Demographics, longitudinal pulmonary function and quantitative CT metrics were compared using descriptive statistics. Linear mixed models, and Cox analyses adjusted for age, gender, BMI, smoking history and treatment with anti‐fibrotics were performed to assess the relationships between baseline DTA, pulmonary function metrics and outcomes. Results: CT scans of 393 participants were analysed, 221 of which had available pulmonary function testing obtained within 90 days of CT. Linear mixed‐effect modelling showed that baseline DTA score was significantly associated with annual rate of decline in forced vital capacity and diffusing capacity of carbon monoxide. In multivariable Cox proportional hazard models, greater extent of lung fibrosis was associated with poorer transplant‐free survival (hazard ratio [HR] 1.20, p < 0.0001) and progression‐free survival (HR 1.14, p < 0.0001). Conclusion: In a multi‐centre observational registry of patients with IPF, the extent of fibrotic abnormality on baseline CT quantified using DTA is associated with outcomes independent of pulmonary function. [ABSTRACT FROM AUTHOR]

Introduction: The relationship between pulmonary function (PF) and mild cognitive impairment (MCI), dementia, and brain pathologies remains unclear. Methods: A total of 1312 dementia‐free participants, including a cognitively intact group (n = 985) and an MCI group (n = 327), were followed for up to 21 years to detect incident MCI and dementia. PF was assessed at baseline with a composite score and tertiled. Over follow‐up, 540 participants underwent autopsies for neuropathological assessment. Results: Compared to the highest PF, the hazard ratios (95% confidence intervals [CIs]) of the lowest PF were 1.95 (1.43‐2.66) for MCI in the cognitively intact group and 1.55 (1.03‐2.33) for dementia in the MCI group. Low PF was further related to Alzheimer's disease pathology (odds ratio [OR] 1.32, 95% CI 1.19‐1.47) and vascular pathology (OR 3.05, 95% CI 1.49‐6.25). Discussion: Low PF increases MCI risk and accelerates MCI progression to dementia. Both neurodegenerative and vascular mechanisms may underlie the PF‐dementia association. [ABSTRACT FROM AUTHOR]

Background: Several risk factors for asthma have been proposed; however, the causality of these associations is sometimes unclear. Mendelian randomization is a powerful epidemiological approach that can help elucidate the causality of risk factors. The aim of the present study was to identify causal risk factors for asthma through Mendelian Randomization studies. Methods: A systematic search of PubMed and EMBASE was conducted, to identify studies investigating risk factors for asthma or respiratory allergies through Mendelian Randomization. When two or more studies investigated the same risk factor a meta‐analysis was conducted. Of 239 studies initially identified, 41 were included. Results: A causal association between adiposity and adult asthma risk was found in 10 out of 12 studies with a summary risk ratio of 1.05 per kg/m2 increase in BMI (95% CI: 1.03–1.07). Puberty timing (n = 3), alcohol (n = 2), and linoleic acid (n = 1) had causal effects on asthma risk, while vitamins/minerals (n = 6) showed no consistent effect on asthma. The effect of smoking on adult asthma conflicted between studies. Several of the significant associations of asthma with immune related proteins (n = 5) and depression (n = 2) investigated through multiple traits analyses could generally benefit from replications in independent datasets. Conclusion: This systematic review and meta‐analysis found evidence for causal effects of adiposity, puberty timing, linoleic acid, alcohol, immune related proteins, and depression on risk of asthma. [ABSTRACT FROM AUTHOR]

Background: T‐cell activation is associated with an adverse outcome in COVID‐19, but whether T‐cell activation and exhaustion relate to persistent respiratory dysfunction and death is unknown. Objectives: To investigate whether T‐cell activation and exhaustion persist and are associated with prolonged respiratory dysfunction and death after hospitalization for COVID‐19. Methods: Plasma and serum from two Norwegian cohorts of hospitalized patients with COVID‐19 (n = 414) were analyzed for soluble (s) markers of T‐cell activation (sCD25) and exhaustion (sTim‐3) during hospitalization and follow‐up. Results: Both markers were strongly associated with acute respiratory failure, but only sTim‐3 was independently associated with 60‐day mortality. Levels of sTim‐3 remained elevated 3 and 12 months after hospitalization and were associated with pulmonary radiological pathology after 3 months. Conclusion: Our findings suggest prolonged T‐cell exhaustion is an important immunological sequela, potentially related to long‐term outcomes after severe COVID‐19. [ABSTRACT FROM AUTHOR]

Background: Obesity and asthma are highly associated, but the mechanisms underlying the association remain unknown. We examined five mediators linking obesity with childhood asthma: (1) pulmonary function impairment, (2) airway inflammation, (3) physical fitness, (4) sleep‐disordered breathing (SDB), and (5) early puberty. Methods: A Mendelian randomization (MR) study with mediation analysis of data obtained from 5965 children as part of the Taiwan Children Health Study. Observational analysis, MR two‐stage least‐squares method, and MR sensitivity analysis were carried out to investigate each causal pathway. Prospective cohort analyses were used to strengthen the findings. Results: The increased asthma risk associated with obesity was found to be mostly mediated through impaired pulmonary function, low physical fitness, and early puberty. In the MR analysis, body mass index was negatively associated with FEV1/FVC and physical fitness index (β = −2.17 and −0.71; 95% CI, −3.92 to −0.42 and −1.30 to −0.13, respectively) and positively associated with early puberty (OR, 1.09; 95% CI, 1.02–1.17). High FEV1/FVC and physical fitness index reduced asthma risk (OR, 0.98 and 0.93; 95% CI, 0.97–0.99 and 0.88–0.98, respectively), whereas SDB and early puberty increased the risk of asthma (OR, 1.03 and 1.22; 95% CI, 1.01–1.05 and 1.05–1.42, respectively). Temporal causality was strengthened in prospective cohort analyses. The three main mediators were low physical fitness, impaired pulmonary function, and early puberty, with mediation proportions of 73.76%, 61.63%, and 27.66%, respectively. Conclusions: Interventions promoting physical fitness and pulmonary function might effectively reduce obesity‐induced asthma risk. [ABSTRACT FROM AUTHOR]

Introduction/aims: Pulmonary decline is a major issue in patients with Duchenne muscular dystrophy (DMD). Eteplirsen is a United States-approved treatment for patients with DMD and exon 51 skip-amenable mutations. Previous analyses have shown that eteplirsen is associated with a statistically significant attenuation of pulmonary decline. In this study we evaluate the effect of eteplirsen treatment from newly available data sources on pulmonary function over time in patients with DMD.Methods: We used a post hoc pooled analysis to compare the percentage of predicted forced vital capacity (FVC%p) and projected time with pulmonary function milestones in patients with DMD and exon 51 skip-amenable mutations receiving eteplirsen (Studies 204 and 301) or standard of care (SoC; Cooperative International Neuromuscular Research Group Duchenne Natural History Study). A mixed model for repeated-measures framework was applied to evaluate the impact of eteplirsen.Results: An average annual rate of FVC%p decline for eteplirsen-treated patients was estimated to be 3.47%, a statistically significant attenuation from the 5.95% rate of decline estimated in SoC patients (P = .0001). Using linear extrapolations of the model-estimated decline in FVC%p, the attenuation in FVC%p decline for eteplirsen-treated patients corresponded to a delay of 5.72 years in time to needing continuous ventilation, 3.31 years in time to needing nighttime ventilation, and 2.11 years in time to needing a cough assist device compared with SoC patients.Discussion: The attenuation of FVC%p decline suggests that eteplirsen-treated patients had statistically significant and clinically meaningful attenuations in pulmonary decline compared with SoC patients. [ABSTRACT FROM AUTHOR]

Background: Few data are available in Asian children regarding the validity of cord blood immunoglobulin E (IgE) in predicting allergic sensitization and pulmonary function. The relationship between cord blood IgE and fraction of exhaled nitric oxide (FeNO) remains unknown. This study investigated the associations of cord blood IgE with allergic sensitization, FeNO, pulmonary function, and allergic diseases in Asian children. Methods: Five hundred and sixty‐six Asian children with valid cord blood IgE measurements at birth participated a 6‐year follow‐up visit including a questionnaire, serum total and allergen‐specific IgE, FeNO measurement, and spirometry. Regression‐based analyses with covariates adjustment were applied. Results: Cord blood IgE levels were significantly associated with FeNO levels (β = 0.131, p <.001) and serum total IgE levels (β = 0.325, p <.001). Cord blood IgE levels were positively associated with allergic sensitization (adjusted odds ratio [AOR] = 2.22, p <.001), and sensitization to mites (p =.002), animals (p =.023), and foods (p =.048). Subjects with cord blood IgE ≥0.24 kU/L (the optimal cutoff) were significantly associated with an increased risk of allergic sensitization (AOR = 2.63, p <.001) and asthma (AOR = 2.35, p =.024) than those with cord blood IgE <0.24 kU/L. Subjects with cord blood IgE ≥0.24 kU/L had significantly higher FeNO levels than those with cord blood IgE <0.24 kU/L (p =.028). There were no significant associations between cord blood IgE levels and pulmonary function parameters. Conclusion: Cord blood IgE ≥0.24 kU/L predicts allergic sensitization, FeNO elevation, and asthma among Asian schoolchildren, suggesting cord blood IgE would be useful for identifying newborns at risk of subsequent allergic sensitization and allergic airway inflammation. [ABSTRACT FROM AUTHOR]

The association of poor pulmonary function (PF) with cognitive trajectories and structural brain differences remains unclear. Within the Rush Memory and Aging Project, 1377 dementia‐free subjects were followed up to 21 years. PF was assessed with a composite score measured at baseline. Global and domain‐specific cognitive function was assessed annually constructed from 19 cognitive tests. A subsample of 351 participants underwent brain magnetic resonance imaging to investigate the cross‐sectional association between PF and structural brain volumes. We found that low PF was related to faster decline in global cognition, and domain‐specific function including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed. In addition, low PF was associated with smaller volumes of total brain, white matter and gray matter, and larger white matter hyperintensities volume. Our results suggest that low PF is associated with faster cognitive decline, and both neurodegeneration and vascular brain lesions may underlie the association. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to investigate the feasibility and efficacy of image‐guided moderately hypofractionated thoracic radiotherapy (hypo‐IGRT) in patients with non–small cell lung cancer (NSCLC) with poor performance status and severely limited pulmonary function and reserve. Methods: Consecutive inoperable patients who had node‐positive, stage IIB‐IIIC (TNM, 8th edition) or recurrent NSCLC, had an Eastern Cooperative Oncology Group performance status ≥1, and had a forced expiratory volume in 1 second (FEV1) ≤1.0 L, had a single‐breath diffusing capacity of the lung for carbon monoxide (DLCO‐SB) ≤40% and/or on long‐term oxygen therapy were analyzed. All patients received hypofractionated IGRT to a total dose of 42.0 to 49.0 Gy/13 to 16 fractions (2.8‐3.5 Gy/fraction) (equivalent dose in 2‐Gy fractions/biologically effective dose [α/β = 10] = 45.5‐55.1 Gy/54.6‐66.2 Gy) alone. Patients were monitored closely for nonhematological toxicity, which was classified per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Results: Between 2014 and 2021, 47 consecutive patients with a median age of 72 years (range, 52.2‐88 years) were treated. At baseline, the median FEV1, vital capacity, and DLCO‐SB were 1.17 L (range, 0.69‐2.84 L), 2.34 L (range, 1.23‐3.74 L), and 35% predicted (range, 13.3%‐69.0%), respectively. The mean and median planning target volumes were 410.8 cc (SD, 267.1 cc) and 315.4 cc (range, 83.4‐1174.1 cc). With a median follow‐up of 28.9 months (range, 0.5‐90.6 months) after RT, the median progression‐free survival (PFS)/overall survival (OS) and 6‐ and 12‐month PFS/OS rates were 10.4 months (95% CI, 7‐13.8 months)/18.3 months (95% CI, 9.2‐27.4 months), 70%/89.4%, and 38.8%/66%, respectively. Treatment was well tolerated with only 1 case each of grade 3 pneumonitis and esophagitis. No toxicity greater than grade 3 was observed. Conclusions: Patients with inoperable node‐positive NSCLC, a poor performance status, and severely limited lung function can be safely and effectively treated with individualized moderately hypofractionated IGRT. The achieved survival rates for this highly multimorbid group of patients were encouraging. In this article, the knowledge gap between the management of patients with unfavorable risk factors and severely limited pulmonary function and reserve (forced expiratory volume in 1 second ≤1 L and/or single‐breath diffusing capacity of the lung for carbon monoxide ≤40% predicted and/or on long‐term oxygen therapy) is addressed. In light of encouraging results, a clinical pathway is proposed for the management of these high‐risk patients. [ABSTRACT FROM AUTHOR]

Background: Although coronavirus disease 2019 (COVID‐19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long‐term respiratory dysfunction remains unknown. Methods: Plasma was collected during hospital admission and after 3 months from the NOR‐Solidarity trial (n = 181) and analyzed for markers of gut barrier dysfunction and inflammation. At the 3‐month follow‐up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO). Rectal swabs for gut microbiota analyses were collected (n = 97) and analyzed by sequencing the 16S rRNA gene. Results: Gut microbiota diversity was reduced in COVID‐19 patients with respiratory dysfunction, defined as DLCO below the lower limit of normal 3 months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide‐binding protein (LBP) were strongly associated with respiratory failure, defined as pO2/fiO2 (P/F ratio) <26.6 kPa. LBP levels remained elevated during and after hospitalization and were associated with low‐grade inflammation and respiratory dysfunction after 3 months. Conclusion: Respiratory dysfunction after COVID‐19 is associated with altered gut microbiota and persistently elevated LBP levels. Our results should be regarded as hypothesis generating, pointing to a potential gut–lung axis that should be further investigated in relation to long‐term pulmonary dysfunction and long COVID. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) patients have lower pulmonary function, respiratory and peripheral muscle strength values when compared to the general population, which reflects negatively in the quality of life (QoL). The aim of this study was to compare the pulmonary function, respiratory and peripheral muscle strength, and QoL between CKD patients and healthy individuals. Cross‐sectional study with a consecutive sample of 39 individuals separated into three groups: nondialysis‐dependent CKD in stage 5 (CKD‐5), HD group (CKD‐HD), and healthy individuals. The tests performed were spirometry, manovacuometry, handgrip strength (HGS), and Medical Outcomes Short‐Form Health Survey (SF‐36). A significant difference between groups was observed in forced expiratory volume in 1 second (FEV1) and its predicted value (p = 0.004 and p < 0.001, respectively), forced vital capacity (FVC), and its predicted value (p = 0.008 and p < 0.001, respectively), peak expiratory flow (PEF) and its predicted value (p = 0.004 and p < 0.001, respectively), maximal inspiratory pressure (MIP) and its predicted value (p = 0.022), maximal expiratory pressure (MEP) and its predicted value (p = 0.030 and p = 0.009, respectively) in which CKD‐5 presented the worst values, followed by CKD‐HD and healthy group. The CKD‐5 had worse pulmonary function, respiratory muscle strength, and QoL. Moreover, CKD‐HD also showed some impairment in pulmonary function and QoL when compared with healthy individuals. Even with the peripheral muscle strength preserved, its decrease is proportional to the pulmonary impairment in the evaluated CKD patients. [ABSTRACT FROM AUTHOR]

Introduction: Many confounding factors such as sex, age, and body mass index (BMI) affect pulmonary function parameters, but there are limited data about the direct and/or indirect effects of small airway function on lung function for differences in confounding factors. Objectives: This study aimed to use structural equation model (SEM) to explain the influence of the confounding factors (age, sex, and BMI) on the relationship between small airway function and lung function in patients with lung cancer. Methods: A cross‐sectional observational study was conducted in a single medical center. Subjects were assessed; small airway function was specified by MEF25% and MEF50%; lung function by FVC; pulmonary obstruction by FEV1, FEV1%, and FEV1/FVC; and PEF and PEF% reflected the strength of abdominal muscles. The measurement model was analyzed by confirmatory factor analysis. The SEM was conducted to analyze the structural models of the effects of the confounding factors. Results: In the measurement model, variables were fit to their domains, the path linking age and sex to pulmonary obstruction was positive and statistically significant, and the path linking sex to muscle strength was also positive and statistically significant. Muscle strength positively and significantly mediates the path between sex and FVC. As a moderator, BMI increased the effects of small airway function on FVC. Conclusion: Age and sex were directed to pulmonary obstruction, and muscle strength as a mediator between sex and lung function was novel, and BMI adjusted the effects of small airway function on FVC. [ABSTRACT FROM AUTHOR]

Background: We tested the hypothesis that multiple obesity‐related risk factors (obesity, physical activity, cardiopulmonary physical fitness, sleep‐disorder breathing (SDB), and sleep quality) are associated with childhood asthma using a Mendelian randomization (MR) design. Furthermore, we aim to investigate whether these risk factors were associated with incident asthma prospectively. Methods: In total, 7069 children aged 12 from the Taiwan Children Health Study were enrolled in the current study. Cross‐sectional logistic regression, one‐sample MR, summary‐level MR sensitivity analyses, and prospective survival analyses were used to investigate each causal pathway. Results: In MR analysis, three of the five risk factors (obesity, SDB, and sleep quality) were associated with asthma, with the highest effect sizes per inter‐quartile range (IQR) increase observed for sleep quality (odds ratio [OR] = 1.42; 95% confidence interval [CI]: 1.06 to 1.92) and the lowest for obesity (OR = 1.08; 95% CI: 1.00–1.16). In the prospective survival analysis, obesity showed the highest risk of incident asthma per IQR increase (hazard ratio [HR] = 1.28; 95% CI: 1.05 to 1.56), followed by SDB (HR = 1.18; 95% CI: 1.08 to 1.29) and sleep quality (HR = 1.10; 95% CI: 1.03 to 1.17). Conclusion: Among the examined factors, the most plausible risk factors for asthma were obesity, SDB, and poor sleep quality. For the prevention of childhood asthma, relevant stakeholders should prioritize improving children's sleep quality and preventing obesity comorbidities such as SDB. [ABSTRACT FROM AUTHOR]

Malnutrition plays a crucial role in pulmonary hypertension (PH). The prognostic nutritional index (PNI) is a reliable indicator for nutritional status assessment. However, its relationship with mortality risk in PH patients has not yet been investigated. This study analyzed data from the Patient Registry for Primary PH. PNI was calculated through albumin and lymphocyte counts. Subjects with missing data for PNI calculation were excluded. The primary endpoint was all‐cause mortality. Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Of the 317 patients records available in the registry, we finally included 136 patients. The average age of the included subjects was 40.56 (14.91) years and 63.24% (86/136) were female. In our analysis of Cox regression, per 1‐point increment of PNI was associated with 4% decreased risk of mortality in PH patients (age‐ and sex‐adjusted HR: 0.96, 95% CI: 0.93–0.98, p = 0.002). We further categorized these subjects by quartiles of PNI. Compared to quartile 4, the age‐ and sex‐adjusted HRs of death for quartiles 1, 2, and 3 were 2.39 (95% CI: 1.21–4.72, p = 0.01), 2.25 (95% CI: 1.15–4.39, p = 0.02), and 1.72 (95% CI: 0.84–3.52, p = 0.14). In addition, logistic regression analyses suggested a positive correlation of PNI with total lung capacity (β = 0.98, p = 0.002) and forced expiratory volume in 1 min (β = 1.53, p = 0.03). This study demonstrates that low PNI was associated with an increased risk of death in PH patients. These findings help to enlighten our understanding of the nutritional status and adverse outcomes in PH patients. [ABSTRACT FROM AUTHOR]

Background: Cadmium is a ubiquitous toxic heavy metal and environmental toxicant. Inflammation exerts central roles in the process of chronic obstructive pulmonary disease (COPD). However, few epidemiological studies on the correlation between cadmium exposure and COPD are available. The aim of this study was to evaluate the correlations among serum cadmium, inflammatory cytokines and pulmonary function in COPD patients. Methods: All 940 COPD patients were finally recruited in this study. Demographic characteristics and clinical information were extracted. Fasting serum was collected. Serum cadmium was detected through graphite furnace atomic absorption spectrophotometry. Serum inflammatory cytokines were measured using enzyme‐linked immunosorbent assay. Results: All patients were classified into three groups according to the tertile division of serum cadmium concentration: low (<0.77 μg/L, L), medium (0.77–1.01 μg/L, M), and high (1.01 μg/L, H). Logistic regression analysis found that serum cadmium was inversely correlated with pulmonary function before and after adjusted confounding variables. When stratified by gender, serum cadmium was still negatively correlated with pulmonary function in COPD patients. Moreover, higher serum cadmium elevated CAT (COPD Assessment Test) score before and after adjusted confounding variables. Though a non‐linear association between serum cadmium and inflammatory cytokines, serum cadmium was positively associated with inflammatory cytokines (TNF‐α and MCP‐1). TNF‐α and MCP‐1 exerted a partial mediator in the association between cadmium exposure and pulmonary function decline in COPD patients. Conclusions: Serum cadmium concentration is inversely correlated with pulmonary function among COPD patients. Inflammatory cytokines may be important mediators for cadmium‐induced pulmonary function decline in COPD patients. [ABSTRACT FROM AUTHOR]

Summary: Adults with obesity exhibit a restrictive pattern, whereas children with obesity exhibit an obstructive pattern. However, the transition process remains unclear. We performed a systematic search for studies reporting on body mass index and pulmonary function in children. The main outcomes were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and their ratio (FEV1/FVC). We compared individuals with overweight or with obesity with individuals with normal weight. Random‐effects models were used to calculate pooled estimates. A total of 17 studies were included. Individuals with obesity had a lower FEV1/FVC ratio (mean difference [MD] = −3.61%; 95% confidence interval [CI] = −4.58%, −2.64%) and a higher percent‐predicted FVC (MD = 3.33%; 95% CI = 0.79%, 5.88%) than those with normal weight. Obesity impaired pulmonary function in the obstructive pattern during childhood to young adulthood, and the maximum obstruction was observed at the age of 16 years in boys and 20 years in girls. The effects attenuated at approximately 30 years and then shifted to the restrictive pattern after 35 years of age in men and 40 years in women. The effects of obesity on pulmonary function change from the obstructive pattern in childhood to the restrictive pattern in adulthood. [ABSTRACT FROM AUTHOR]

Background: With the advent of high‐resolution chest imaging, the number of patients diagnosed with multiple primary lung cancers is increasing. For the treatment of multiple lung cancers, a surgical procedure that preserves pulmonary function while ensuring curability is required. Methods: The study population included 85 patients with synchronous multiple primary lung cancer who received surgical resection between January 2010 and September 2020. Patients with synchronous lung cancer within the same lobe were excluded, and only patients with ≥2 involved lobes were included. The postoperative pulmonary function was examined at 3–6 months after the surgery. Results: Sixty‐seven patients had cancers within the ipsilateral lobe, and 18 patients had cancers in bilateral lobes. Seventy‐six patients (89.4%) underwent combination surgery with limited resection (e.g., segmentectomy and wedge resection). The preoperative pulmonary functions (mean VC/%VC, mean FEV1/%FEV1, and mean %DLCO) were 3.06 L/100.2%, 2.23 L/96.1%, and 117.2%, respectively, and the postoperative pulmonary functions were 2.45 L/81.4%, 1.87 L/81.2%, and 102.6%. In each parameter, the predicted reductions of pulmonary function were almost the same as the predicted values. The 5‐year survival rate was 85.0%. The 5‐year survival rate according to the most advanced pathological stage was 94.9% for stage I disease, and 62.6% for stage ≥II, which was a significant difference (p < 0.001). Conclusions: Surgical treatment including limited resection, especially segmentectomy and wedge resection, for synchronous multiple primary lung cancer can preserve pulmonary function while ensuring curability. [ABSTRACT FROM AUTHOR]

Background: Impaired lung function is a well‐known risk factor in cardiac surgery patients and reduced forced expiratory volume in 1 second (FEV1) is associated with increased mortality. However, there is limited knowledge regarding the influence of impaired diffusing capacity of the lungs for carbon monoxide (DLCO) in unselected cardiac surgery patients. The aim of this study was to investigate the association of impaired DLCO and/or reduced FEV1 on post‐operative mortality and morbidity in cardiac surgery patients. Methods: In a prospective cohort study, 390 patients scheduled for elective cardiac surgery underwent preoperative lung function test including spirometry and DLCO measurements. We defined reduced FEV1 as FEV1 below lower limit of normal (LLN) and impaired DLCO as DLCO <60% of predicted. Results: Mortality within 1 year (90‐570 days) was significantly higher in patients with impaired DLCO (12% vs 3%, P =.010) and with reduced FEV1 (9% vs 3%, P =.028). Mortality was higher in patients with impaired DLCO both in the presence and absence of FEV1 < LLN. In multivariate analysis, only impaired DLCO [OR: 3.3, 95% confidence interval (CI) 1.4‐7.5; P =.005] and age (OR: 1.1 per year, 95% CI 1.0‐1.2; P =.001) were independent predictors of the combined outcome of mortality and prolonged intensive care unit (ICU) stay. Impaired DLCO was also associated with post‐operative respiratory complications. Conclusion: In patients undergoing elective cardiac surgery, preoperative impaired FEV1 and DLCO were associated with increased mortality and morbidity. In multivariate analysis, only DLCO and age were independent predictors of a combined outcome of mortality and prolonged ICU stay. [ABSTRACT FROM AUTHOR]

Summary: The spirometry is considered a preclinical tool for the evaluation of the respiratory system. The formal lung volumes measurement and health status lung system are made using spirometry. Artificial neural network (ANN) has been introduced in solving complex problems in a large number of different settings, including medical diagnosis support system as predictive power. An objective of this research was intended to investigate the development of a new decision support system (DSS) using ANN modeling approaches and algorithms to predict pulmonary function in people. The spirometry data and general characteristics, anthropometric data, and body composition parameters (N = 130) were obtained from subjects. The classification of pulmonary function was performed by the multi‐layer perceptron (MLP) model. Findings show that the MLP model is capable of classifying respiratory abnormalities in different people. The ANN model was totally 93.6%, 92.3%, 84.6%, and 91.5% successful in correctly classified in training, validation, test, and all data, respectively. Also, a DSS tool was created that allows the evaluation and classification of the results of spirometry data. It appears that ANNs are useful in classification pulmonary function. [ABSTRACT FROM AUTHOR]

The aims of the study were to evaluate the prevalence of sleep‐disordered breathing (SDB) by using polysomnography (PSG) in children with MPS IVA and MPS VI who underwent enzyme replacement therapy (ERT) and to analyze the effect on SDB of having upper airway surgery, pulmonary functions, and exercise capacity. A retrospective cross‐sectional study was conducted on patients with MPS IVA (n:17) and MPS VI (n:11) aged under 19 years who underwent polysomnography. Descriptive and nonparametric analyses were performed for demographic, PSG, pulmonary function and exercise capacity variables. The frequency of sleep apnea in the study sample was 85.7% (24/28). Four patients (14.3%) had no sleep apnea, 15 (53.6%) had mild, and nine (32.1%) had moderate‐to‐severe sleep apnea. Two patients (7.1%) had central sleep apnea and 22 had obstructive sleep apnea (OSA) (78.6%). Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were negatively correlated to apnea‐hypopnea index (AHI) (r = −0.594, p =.009; r = −0.636, p =.005, respectively). Despite ERT and previous upper airway surgery, the prevalence of OSA was high in patients with MPS IVA–MPS IV, emphasizing the importance of PSG screening for sleep disorders. Pulmonary function tests may be useful for predicting sleep apnea in patients with MPS IVA and MPS VI. [ABSTRACT FROM AUTHOR]

Objectives: Chronic obstructive pulmonary disease (COPD) patients have higher laryngopharyngeal reflux (LPR)‐related symptom incidence. But LPR treatment is empirical. We aimed to determine the frequency of LPR, diagnosed by 24‐hour Dx‐pH monitoring, among acute exacerbations of COPD (AECOPD) patients with Reflux Symptom Index (RSI) ≥13 and investigate proton pump inhibitor (PPI) treatment effect on LPR, COPD symptoms, and pulmonary function. Methods: From January 2016 to September 2017, 102 AECOPD patients with RSI ≥13 were enrolled. COPD assessment test (CAT), mMRC dyspnea scale, pulmonary function tests, and 24‐hour Dx‐pH monitoring were performed. The Ryan score was evaluated by using the Dx‐pH DataView Lite software, which identifies patients with abnormal pharyngeal pH environments. Associations among RSI, pulmonary function test results, and Ryan score parameters were evaluated. The abovementioned assessments were reperformed after treatment, and pre‐ and posttreatment data were compared. Results: Of the 102 eligible patients, 49 (48.04%) were diagnosed with LPR based on Ryan score. Percentage of the forced expiratory volume at 1 second (FEV1%) was significantly worse in Ryan‐positive than in Ryan‐negative AECOPD patients. There were significant negative correlations between FEV1% and Ryan score (r = −0.394, P < 0.001), FEV1% and % time below pH threshold (r = −0.371, P < 0.001) in upright position but not in supine position. There was no significant correlation between RSI and Ryan score parameters. There were significant improvements in RSI, mMRC, CAT, and FEV1% in Ryan‐positive AECOPD patients after PPI and basic treatments. Conclusion: Study results indicate unreliability of RSI threshold for LPR diagnosis. Combination of symptoms, endoscopic findings, and 24‐hour Dx‐pH monitoring is recommended for LPR diagnosis and PPI treatment decisions, especially in difficult‐to‐control or severe COPD patients. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to quantify the effect of endoscopic sinus surgery on pulmonary function in patients with cystic fibrosis and chronic rhinosinusitis. Methods: The PubMed, MEDLINE, Cochrane Library, and Embase databases were searched for studies published in English, without any language and time restrictions from their inception to March 1, 2020. Studies examining pulmonary function outcomes in patients with cystic fibrosis and chronic rhinosinusitis following endoscopic sinus surgery were included. Primary outcomes were pulmonary function tests, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow between 25% and 75% of vital capacity (FEF25‐75). Results: A total of 12 studies with 570 patients were included for data extraction and meta‐analysis. For FEV1 (%), the summarized mean difference (MD) was −6.92 (95% confidence interval [CI] = −19.67 to 5.83, P =.29) and 0.70 (95% CI = −3.81 to 5.21, P =.76) for the postoperative results after 6 months and 12 months, respectively. The pooled MDs for FVC (%) and FEV1/FVC ratio (%) for the postoperative results after 6 months were 0.60 (95% CI = −4.12 to 5.31, P =.80) and −1.29 (95% CI = −6.14 to 3.55, P =.60). Conclusion: Endoscopic sinus surgery in chronic rhinosinusitis patients with cystic fibrosis did not improve the pulmonary function in chronic rhinosinusitis patients with cystic fibrosis. More prospective studies and meta‐analyses addressing the same topic are needed in the future. Laryngoscope, 131:720–725, 2021 [ABSTRACT FROM AUTHOR]

Background: Cystic fibrosis (CF) causes malabsorption of nutrients that exacerbate pulmonary problems. Nutritional interventions can improve pulmonary functions. We aimed to evaluate the effects of nutritional intervention in CF patients with malnutrition, and to determine if there is a correlation between nutritional status and pulmonary functions. Methods: The study included 143 CF patients (67 females) with a mean 2 year follow‐up time. Patients' sociodemographic data, presenting symptoms and history were recorded. Height‐for‐age, weight‐for‐age, weight‐for‐length/height (WFL/H), and body mass index (BMI) were calculated in all patients. Patients were grouped as well nourished, mild malnutrition, moderate malnutrition, and severe malnutrition. These four groups were compared in terms of pulmonary function test results, lung infections, and the hospitalization rate. Results: Among the patients with a WFL/H or BMI z‐scores that decreased, the frequency of lung infection was 74.1% and the hospitalization rate was 40.7%, versus 34% and 12.3%, respectively among the patients with a WFL/H or BMI z‐scores that increased. The difference was significant (P = 0.02 and P = 0.01, respectively). The difference in bacterial lung infections differed significantly between the four nutritional status groups (P = 0.002). Patients in the well‐nourished group had significantly higher pulmonary function test scores than the other groups. The forced expiratory volume in the first second differed significantly between the patients with and without an increase in the WFL/H or BMI z‐scores (P = 0.001). Conclusions: The appropriate nutritional intervention to pediatric CF patients with malnutrition, decrease the frequency of lung infections, and improve respiratory function. [ABSTRACT FROM AUTHOR]

Background: With an increase in smartphone usage, constant neck flexion can lead to improper posture, which may impact on lung function. Therefore, the purpose of this study was to examine and compare the craniovertebral angle (CVA) and lung function between addicted and non‐addicted boys and girls aged between 8–13 years who use smartphones for long periods of time. Methods: A cross‐sectional study was conducted on 24 boys and 26 girls (mean age 10.5 ± 1.6 years and body mass index 18.6 ± 3.0 kg/m2). Participants were assigned to two groups based on their scores on the Smartphone Addiction Scale‐Short Version (SAS‐SV) for Adolescents: addicted group (score > 32, n = 32) and non‐addicted group (score ≤ 32, n = 18). The outcome variables were CVA, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), maximal voluntary ventilation (MVV), maximum inspiratory pressures (PImax), and maximum expiratory pressures (PEmax). Results: There was a significant difference in mean CVA between addicted and non‐addicted boys (49.4 ± 6.7 vs 55.5 ± 7.6, η2 = 0.9, P = 0.03) and girls (47.3 ± 6.3 vs 52.9 ± 6.1, η2 = 0.9, P = 0.02). Mean FVC, FEV1, and FEV6 were significantly lower in addicted versus non‐addicted boys (P = 0.04, P = 0.05, and P = 0.02, respectively). PImax was significantly less in addicted compared to non‐addicted girls (55.2 ± 16.4 vs 65.3 ± 13.8, η2 = 0.7, P = 0.05). Conclusion: Our findings showed that children addicted to smartphones (when using the SAS‐SV as an indicator for addiction) revealed lower CVA and lung function results. Therefore, education on proper posture while holding smartphones is essential to the children's postural and lung function status. [ABSTRACT FROM AUTHOR]

Background: Several health conditions are associated with cement dust exposure; obstructive and restrictive lung disorders are the most common consequences. The aims of this study were to assess the pulmonary function of cement factory workers and to determine the distribution of respiratory consequences resulting from dust inhalation. Methods: A cross‐sectional study with convenience sampling was undertaken from December 2019 to March 2020. A total of 97 (response rate, 92.4%) nonsmoking male cement workers were recruited and compared with 97 apparently healthy volunteers. A spirometer was used to measure forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and their ratio (FEV1/FVC). The measured parameters were interpreted according to American Thoracic Society/European Respiratory Society guidelines. Results: Significant reductions were observed in pulmonary function parameters of cement factory workers compared to controls (FVC 4.03 vs. 4.65 L in controls; FEV1 3.06 vs. 3.95 L in controls; p < 0.001 for both comparisons). A significant variation was observed in the prevalence of spirometric patterns between the two participating groups. Ninety (92.8%) controls had normal respiratory function with no defects, compared with only 25 (25.8%) of the cement workers. Restriction was the most common respiratory problem, with a greater prevalence in the cement workers (44 [45.4%]) compared to six (6.2%) controls. Conclusions: Cement factory workers showed decreased lung function and abnormal spirometric patterns which we attribute to dust inhalation. These workers should have periodic medical examinations and regular rotations through different factory departments to minimize the pulmonary hazards of cement dust. [ABSTRACT FROM AUTHOR]

Cannabis is one of the world's most widely used recreational drugs and the second most commonly smoked substance. Research on cannabis and the lungs has been limited by its illegal status, the variability in strength and size of cannabis cigarettes (joints), and the fact that most cannabis users also smoke tobacco, making the effects difficult to separate. Despite these difficulties, the available evidence indicates that smoking cannabis causes bronchitis and is associated with changes in lung function. The pattern of effects is surprisingly different from that of tobacco. Whereas smoking cannabis appears to increase the risk of severe bronchitis at quite low exposure, there is no convincing evidence that this leads to chronic obstructive pulmonary disease. Instead, cannabis use is associated with increased central airway resistance, lung hyperinflation and higher vital capacity with little evidence of airflow obstruction or impairment of gas transfer. There are numerous reports of severe bullous lung disease and pneumothorax among heavy cannabis users, but convincing epidemiological data of an increased risk of emphysema or alveolar destruction are lacking. An association between cannabis and lung cancer remains unproven, with studies providing conflicting findings. [ABSTRACT FROM AUTHOR]

Independent of heat stress and dehydration, pre-menopausal females have attenuated increases in blood pressure in response to metaboreflex activation from skeletal and respiratory muscle afferents compared to males. Keywords: dehydration; exercise pressor reflex; heat wave; older adults; pulmonary function; respiratory metaboreflex EN dehydration exercise pressor reflex heat wave older adults pulmonary function respiratory metaboreflex 2759 2760 2 07/18/23 20230715 NES 230715 The cardiovascular adjustments required to meet the metabolic demands of the working muscles during exercise are largely mediated by responses from the autonomic nervous system that are dependent on the mode of exercise performed (e.g. dynamic, isometric) (Cui et al., [1]; Smith et al., [4]). [Extracted from the article]

Background & Aims: The association between nonalcoholic fatty liver disease (NAFLD) and pulmonary function remains elusive because of the heterogeneous spectrum and inaccurate diagnostic methods of NAFLD, and insufficient pulmonary function data. We conducted this study to identify the association between histological severity of NAFLD and pulmonary function. Methods: This study included patients ≥18 years old with baseline pulmonary function data between August 2014 and July 2019 within a biopsy‐evaluated prospective NAFLD cohort. Cross‐sectionally, pre‐/post‐bronchodilator spirometric data with diffusing capacity (DLCO) were compared according to histological severity of NAFLD in the various demographic and metabolic subgroups. Multivariable‐adjusted analysis revealed specific histological features associated with reduced pulmonary function. Results: In a total of 420 patients with biopsy‐proven NAFLD, pre‐/post‐bronchodilator forced vital capacities (FVCs; a percentage of the predictive value) were inversely correlated with histological severity of NAFLD. Conversely, pre‐bronchodilator forced expiratory volume in 1 second (FEV1)/FVC was positively correlated with NAFLD severity. Post‐bronchodilator FVC (%) decreased and DLCO/alveolar volume (VA) increased linearly with worsening histological severity of NAFLD in multivariable analysis. In particular, fibrosis stage remained a significant independent predictor of decreased post‐bronchodilator FVC (%) (β‐coefficient, 4.41; 95% confidence interval [−8.39, −0.43]; P =.031) even after adjusted for clinical variables, exclusively in age <65 years, female, never‐smoker and nonchronic obstructive pulmonary disease subgroups. Conclusions: Pulmonary function deteriorates with worsening histological severity of NAFLD, especially at the fibrosis stage. The common pathogenesis of reduced pulmonary function and NAFLD fibrosis progression should be further explored. [ABSTRACT FROM AUTHOR]

Background and Aim: The eucapnic voluntary hyperventilation (EVH) testing is a diagnostic tool for diagnostics of exercise‐induced bronchoconstriction; while the testing has become more common among children, data on the test's feasibility among children remain limited. Our aim was to investigate EVH testing feasibility among children, diagnostic testing cut‐off values, and which factors affect testing outcomes. Methods: We recruited 134 patients aged 10–16 years with a history of exercise‐induced dyspnoea and 100 healthy control children to undergo 6‐min EVH testing. Testing feasibility was assessed by the children's ability to achieve ≥70% of the target minute ventilation of 30 times forced expiratory volume in 1 s (FEV1). Bronchoconstriction was assessed as a minimum of 8%, 10%, 12%, 15% or 20% fall in FEV1. Patient characteristics were correlated with EVH outcomes. Results: Overall, 98% of the children reached ≥70%, 88% reached ≥80%, 79% reached ≥90% and 62% reached ≥100% of target ventilation in EVH testing; of children with a history of exercise‐induced dyspnoea, the decline percentages were as follows: 24% (≥8% fall), 17% (≥10% fall), 10% (≥12% fall), 6% (≥15% fall) and 5% (≥20% fall) in FEV1, compared to 11%, 4%, 3%, 1% and 0% among the healthy controls, respectively. Healthy controls and boys performed testing at higher ventilation rates (p <.05). Conclusion: Eucapnic voluntary hyperventilation testing is feasible among children aged 10–16 years and has diagnostic value in evaluating exercise‐induced dyspnoea among children. A minimum 10% fall in FEV1 is a good diagnostic cut‐off value. Disease status appears to be important covariates. [ABSTRACT FROM AUTHOR]

Background: Cardiorespiratory impairments are considered the main cause of mortality in the late stages of Parkinson's. Aerobic exercise has been shown to improve pulmonary function in asthmatic patients and in healthy people. However, effects of aerobic exercise on cardiopulmonary function in people with Parkinson's have not been investigated. Therefore, this study aimed to review the effects of aerobic exercise on cardiopulmonary function in people with Parkinson's. Methods: A systematic search was conducted using MEDLINE, AMED, CINHAL Plus, and relevant associated keywords, from January 1970 to January 2020. Inclusion criteria for the studies were: aerobic exercise as part of the intervention, pulmonary function test, and/or cardiopulmonary exercise test as outcome measures. Results: In total, 329 citations were identified from the search, of which nine were included in this review. In general, aerobic exercise was found to have positive effects on cardiac function for people with Parkinson's, but there is a lack of studies on the effects of aerobic exercise on pulmonary function. Conclusion: People with early stages of Parkinson's may experience positive effects of aerobic exercise on cardiac fitness. Further research is needed in this area, particularly into the effects of aerobic exercise on pulmonary function in early stages of the disease. [ABSTRACT FROM AUTHOR]

Aims: Heart failure with preserved ejection fraction (HFpEF) is one of the major diagnoses in dyspnoeic subjects, and H2FPEF score enables robust differentiation of HFpEF. Given ventilatory abnormalities prevail in subjects with HFpEF, the associations between H2FPEF score and pulmonary function remain to be elucidated. Methods and results: Subjects who presented with exertional dyspnoea and had left ventricular ejection fraction of >50% were eligible for this study. Total lung capacity, forced expiratory volume in the 1 s, and forced vital capacity (FVC) were obtained by pulmonary function tests. Pulmonary artery systolic pressure (PASP), the ratio of early ventricular filling flow velocity to the septal mitral annulus tissue velocity (E/e'), and left ventricular mass (LVM) were measured by echocardiogram. Among a total of 5849 participants (65.6 ± 6.4 years, 54% men), 2453 (41.9%) had low H2FPEF score (0 ~ 1) and 160 (2.7%) had high H2FPEF score,6~9 respectively. Subjects with high H2FPEF score were older and had higher proportion of restrictive and obstructive defect, more morbidities, poorer renal function, lower haemoglobin, higher LVM, E/e' ratio, and PASP. During a mean follow‐up duration of 30.0 ± 20.5 months, the H2FPEF score was significantly associated with mortality [hazard ratio and 95% confidence intervals, 1.063(1.010–1.18)], independent of sex, haemoglobin, renal function, LVM, and comorbidities. Conclusions: Either obstructive or restrictive ventilation defects prevail in subjects with high H2FPEF score, indicating chronic obstructive pulmonary disease (COPD) is commonly associated with HFpEF. In addition, H2FPEF score was correlated with long‐term survival in dyspnoeic subjects with or without concomitant diseases of HFpEF and COPD. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the first cause of cancer mortality worldwide. Chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer. An epidemiological survey discovered that the presence of COPD increases the risk of lung cancer by 4.5‐fold. Lobectomy is considered to be the standard surgical method for early stage non‐small cell lung cancer (NSCLC). However, the influence of lobectomy on the loss of pulmonary function has not been fully investigated in NSCLC patients with COPD. Methods: We searched the PubMed database using the following strategies: COPD and pulmonary function test (MeSH term) and lobectomy (MeSH term) from 01 January 1990 to 01 January 2019. We selected the articles of patients with COPD. A total of six studies, including 195 patients with COPD, provided lung function values before and after surgery. Results: Five out of six studies focused on the short‐term change of pulmonary function (within 3–6 months) after lobectomy, and the average loss of FEV1 was 0.11 L (range: −0.33–0.09 L). One study investigated the long‐term change of pulmonary function (within 1–2 years) after lobectomy, and the average loss of FEV1 was 0.15 L (range: −0.29–0.05 L). Conclusions: A short‐term (3–6 months) loss of pulmonary function after operation is acceptable for lung cancer patients with COPD. However, there may be a high risk of postoperative complications in NSCLC patients with COPD. Therefore, surgical treatment needs to be carefully considered for these patients. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to investigate the association between impaired pulmonary function and periodontitis. Materials and Methods: From the Third National Health and Nutrition Examination Survey data, we examined the association between pulmonary function and severity of periodontitis using the univariate and multivariate regression models. Moreover, the association between obstructive or restrictive spirometry patterns and periodontitis status was also determined by multivariable logistic regression analysis. Results: A total of 10,645 participants were included in our study. The values of predicted FEV1%, predicted FVC%, and FEV1/FVC were found to gradually decline with increasing severity of periodontitis (p <.001). Obstructive and restrictive pulmonary functions were significantly associated with severity of periodontitis. Conclusion: Individuals with a greater degree of periodontitis had poor pulmonary function. However, further long‐term cohort studies are required for a comprehensive evaluation. [ABSTRACT FROM AUTHOR]

Introduction: The COPD Assessment Test (CAT) is utilised to evaluate the treatment outcome regarding the health status in idiopathic interstitial pneumonia (IIP). However, the ability of the CAT to evaluate the lung‐specific quality of life in systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) is not established. Therefore, we investigated whether CAT scores can be used to evaluate SSc‐ILD as they are for IIP. Methods: A total of 150 patients with IIP or SSc‐ILD who were evaluated by the CAT were retrospectively assigned to this study. Clinical data at the visit for the CAT were analysed. Results: The forced vital capacity and distance walked during the 6‐minute walk test (6MWD) were significantly correlated with the CAT score for SSc‐ILD and IIP, and the CAT scores were similarly distributed in SSc‐ILD and IIP. The CAT score of SSc‐ILD patients was negatively affected by pulmonary arterial hypertension, but not by corticosteroids, which affected it in IIP patients. CAT scores of patients with either disease receiving home oxygen therapy were poor. In multiple regression analysis, pulmonary arterial hypertension and 6MWD were independent predictors for the CAT score in patients with SSc‐ILD, while corticosteroid administration was selected as an independent factor in patients with IIP. Conclusions: Our study suggests that the CAT can be applied to evaluate the lung‐specific quality of life in SSc‐ILD similar to IIP regarding the pulmonary function, but it should be noted that pulmonary arterial hypertension in SSc‐ILD influences the CAT score. [ABSTRACT FROM AUTHOR]

Background and objective: We recently noted a dramatic increase in the number of patients with accelerated silicosis associated with exposure to artificial stone dust. Therefore, the natural history of artificial stone‐associated silicosis was compared with that of natural stone‐associated silicosis. Methods: A total of 18 patients with artificial stone‐associated silicosis and 63 with natural stone‐associated silicosis were diagnosed sequentially in 2018 and followed up for a period of 6–12 months. Data were collected from clinical charts. Results: The median duration of exposure prior to onset of symptoms of silicosis was shorter for patients who had been exposed to artificial stone dust (6.4 vs 29.3 years, P < 0.01). Four of the 18 patients experienced rapid deterioration in lung function over the follow‐up period, with declines in pre‐bronchodilator FVC of 587 (210–960) mL/year and FEV1 of 625 (360–860) mL/year. GGO, PMF, emphysema and pulmonary artery widening were more frequently observed on computed tomography scans of patients with artificial stone‐associated silicosis than of those with natural stone‐associated silicosis. Approximately 38.9% of the patients with artificial stone‐associated silicosis were lung transplant candidates and 27.8% died, both rates being significantly higher than in patients with natural stone‐associated silicosis (3.2% and 0%, both P < 0.01). Conclusion: Compared to natural stone‐associated silicosis, artificial stone‐associated silicosis was characterized by short latency, rapid radiological progression, accelerated decline in lung function and high mortality. [ABSTRACT FROM AUTHOR]

Background: While respiratory muscle strength is recognized to decline with aging process, the relationship between sarcopenia and pulmonary function remains to be studied. The present study was undertaken to provide a better insight into the comprehension of the relationship between pulmonary function and muscle function (strength and physical performance) using an unselected sample of subjects assessed during the Longevity Check‐up 7+ project. Methods: Look‐up 7+ is an ongoing cross‐sectional survey started in June 2015 and conducted in unconventional settings (i.e. exhibitions, malls, and health promotion campaigns) across Italy. Candidate participants are eligible for enrolment if they are at least 18 years of age and provide written informed consent. Muscle strength was assessed by handgrip strength test, and physical performance was evaluated by chair stand test. Spirometer analysis was performed using the AirSmart system, and the largest forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and peak expiratory flow (PEF) values were collected. Results: The mean age of 925 subjects participating in the Longevity check‐7+ surveys and receiving the spirometer evaluation was 55.6 years (range from 18 to 98 years), and 501 (54%) were women. Overall, both in male and female participants, FVC, FEV1 and PEF positively correlated with handgrip strength and chair stand tests. The receiver operator characteristic curve analysis revealed that the areas under the curves for FVC, FEV1, and PEF were 0.79, 0.80 and 0.80, respectively. Conclusions: The results clearly show that pulmonary function was positively associated with handgrip strength and chair stand tests. Based on this observation, muscle strength, physical performance, and pulmonary function should be recommended as the method of choice for the early detection of individuals at risk of probable sarcopenia and at the same time to better characterized the severity of sarcopenia status. [ABSTRACT FROM AUTHOR]

Background: Pulmonary function is not routinely assessed in patients without respiratory disease and symptoms before surgery, even if they are smokers. We aimed to check whether the new spirometric reference values of the worldwide Global Lung Initiative (GLI) affected the preoperative assessment of lung function in allegedly lung‐healthy patients compared with the still commonly used old predicted values. Methods: Two hundred nineteen allegedly lung‐healthy non‐smokers, past and current smokers were examined by spirometry before elective surgery. The obtained values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC were transformed into z‐scores according to the GLI guidelines. A comparison between the new and old reference values was performed. FEV1 was used for the grading of airway obstruction. Results: One hundred eighty‐three subjects performed the ventilation manoeuvre according to the GLI recommendations and were analysed. Most non‐smokers and past smokers met the new references ranges for spirometric values. Only z‐scores of FEV1/FVC distinguished among all three patient groups, FEV1 between smokers and the other two groups and FVC did not discriminate the groups, irrespective of the reference values used. Airway obstruction was identified in 24% of asymptomatic smokers by z‐scores of FEV1/FVC but in only 14% by the old predicted values. In elderly smokers (>60 years), the corresponding values rose to 50% and 30%. Old predicted values of FEV1 underestimated the degree of airway obstruction mainly in middle‐aged smokers. Conclusion: Allegedly lung‐healthy current smokers showed a higher proportion of preoperatively reduced lung function when z‐scores were used, especially in elderly subjects. [ABSTRACT FROM AUTHOR]