The role of clinical characteristics and pulmonary function testing in predicting risk of pneumothorax by CT-guided percutaneous core needle biopsy of the lung.

BACKGROUND: We aim to analyze the risk factors for pneumothorax associated with computed tomography (CT)-guided percutaneous core needle biopsy (PCNB) of the lung. Whether the lung function characteristics are related to pneumothorax is unclear. METHODS: We retrospectively evaluated 343 patients who received CT-guided pulmonary PCNBs and underwent preoperative pulmonary function testing. Demographical, lesion-related, procedure-related features and histopathological diagnosis, as well as results of pulmonary function test were analyzed as risk factors of pneumothorax RESULTS: Variables associated with higher rate of pneumothorax were location of lesion, presence of emphysema, and dwell time. The proportion of middle lobe, lingular, or lower lobe lesions in pneumothorax group (30/50, 60.0%) is higher than non-pneumothorax group (113/293, 38.6%). The incidence of emphysema in pneumothorax group was significantly higher than that in non-pneumothorax group (34.0% vs. 7.5%). Obstructive pulmonary function abnormalities, not restrictive, mixed ventilation function abnormalities and small airway dysfunction, correlated with pneumothorax. Multivariate logistic regression analysis showed lower location of lesion sampled and presence of emphysema were independent predictors of pneumothorax. Although dwell time, FEV1/FVC ratio, FEF50%, FEF75% and FEF25-75% were significantly correlated with pneumothorax on univariate analysis, these were not confirmed to be independent predictors. CONCLUSIONS: Patients with obstructive pulmonary dysfunction have a higher risk of pneumothorax. Presence of emphysema was the most important predictor of pneumothorax, followed by location of lesion.

Long-term pulmonary function, thoracic pain, and quality of life in patients with one or more rib fractures.

BACKGROUND: Long-term outcomes after rib fractures and the effect of treatment modality or chest wall injury severity on these outcomes remains uncertain. This retrospective cohort study evaluated the long-term pulmonary function, thoracic pain, and quality of life in patients admitted with rib fractures. METHODS: Patients admitted with rib fractures between January 1, 2012, and December 1, 2019, were included. Data on long-term outcomes were collected during one follow-up visit. Patients were stratified by chest wall injury severity (one or two rib fractures, ≥3 rib fractures, or a flail chest) and treatment modality (surgical stabilization of rib fractures [SSRF] or nonoperative management). Multivariable analysis was performed to compare outcomes after SSRF with nonoperative treatment in patients with three or more rib fractures. RESULTS: In total, 300 patients were included. The median follow-up was 39 months (P25-P75, 18-65 months). At follow-up, the corrected forced vital capacity returned to 84.7% (P25-P75, 74.3-93.7) and the forced expiratory volume in 1 second to 86.3% (P25-P75, 75.3-97.0) of the predicted reference values. Quality of life was determined using the Short Form-12 version 2 and EuroQoL-5D-5L. The Short Form-12 version 2 physical and mental component summary were 45 (P25-P75, 38-54) and 53 (P25-P75, 43-60), respectively. The EuroQoL-5D-5L utility score was 0.82 (P25-P75 0.66-0.92) and visual analog scale score 75 (P25-P75 70-85). This indicated a quality of life within normal population ranges. Moderate to severe thoracic pain was reported by 64 (21.3%) patients. Long-term outcomes returned to values within population ranges and were similar across chest wall injury severity and for patients treated with SSRF or nonoperatively. CONCLUSION: While long-term pulmonary function and quality of life recover to values considered normal, subjective thoracic complaints, such as pain and dyspnea, remain frequently present following rib fractures. No effect of chest wall injury severity or treatment modality on long-term outcomes was demonstrated. LEVEL OF EVIDENCE: Therapeutic, level III.

Risk factors associated with postoperative respiratory failure in tuberculous empyema patients.

ABSTRACT: Our objective was to identify independent risk factors for predicting which patients in the Chinese population would likely develop respiratory failure.A descriptive analysis was conducted of demographic and clinical data of patients with tuberculous empyema (TE) admitted to the Beijing Chest Hospital, Capital Medical University between January 2001 and January 2020. Risk factors associated with postsurgical respiratory failure in TE patients were identified based on results of analyses based on univariable and multivariable logistic regression models.A total of 139 TE patients who underwent surgical treatment in the Beijing Chest Hospital, Capital Medical University from January 2001 to January 2020 were enrolled in this study. Cases included 109 male and 30 female patients, with an overall mean age (range 17-73) of 39.3 years. Of 139 TE patients, 26 (18.7%) experienced respiratory failure after surgery. Among significant risk factors for postsurgical respiratory failure, intraoperative blood loss volume greater than 1000 mL had the highest odds ratio value of 6.452. In addition, a pathologic preoperative pulmonary function test result showing a high partial pressure of carbon dioxide level was an independent risk factor for respiratory failure. Moreover, the presence of tuberculosis lesions in the contralateral lung was another significant risk factor for respiratory failure, as determined using multivariate analysis.Respiratory failure is a predominant complication experienced by TE patients undergoing surgery. High intraoperative blood loss, high preoperative high partial pressure of carbon dioxide level, and tuberculosis lesion(s) in the contralateral lung of TE patients were associated with increased risk of postoperative respiratory failure.

Clinical Features and Outcomes of Combined Pulmonary Fibrosis and Emphysema After Lung Transplantation.

BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is recognized as a characteristic syndrome of smoking-related interstitial lung disease that has a worse prognosis than idiopathic pulmonary fibrosis (IPF). However, outcomes after lung transplantation for CPFE have not been reported. The aim of this study is to describe the clinical features and outcomes of CPFE after lung transplantation. RESEARCH QUESTION: What are the clinical features and outcomes of CPFE after lung transplantation? STUDY DESIGN AND METHODS: This is a single-center retrospective cohort study of patients with CPFE and IPF who underwent lung transplantation at our center between January 2011 and December 2016. We defined CPFE as ≥10% emphysema in the upper lung fields combined with fibrosis on high-resolution CT scan. We characterized the clinical features of patients with CPFE and compared their outcomes after lung transplantation with those with IPF. RESULTS: Twenty-seven of 172 (16%) patients with IPF met criteria for CPFE. Severe pulmonary hypertension was present in 16 of 27 (59%) patients with CPFE. On logistic regression analysis, CPFE was significantly associated with primary graft dysfunction (PGD) grade 3 (OR, 3.14; 95% CI, 1.18-8.37; P = .02). On competing risk regression analysis, CPFE was associated with acute cellular rejection (ACR) grade ≥ A2, and chronic lung allograft dysfunction (CLAD) (hazard ratio [HR], 1.89; 95% CI, 1.10-3.25; P = .02; HR, 1.96; 95% CI, 1.02-3.77; P = .04, respectively). Five-year survival was 79.0% for the CPFE group and 75.4% for the IPF group (log-rank P = .684). INTERPRETATION: After transplantation, patients with CPFE were more likely to develop PGD, ACR, and CLAD compared with those with IPF. However, survival was not significantly different between the two groups.

Immunofibrotic drivers of impaired lung function in postacute sequelae of SARS-CoV-2 infection.

BACKGROUNDIndividuals recovering from COVID-19 frequently experience persistent respiratory ailments, which are key elements of postacute sequelae of SARS-CoV-2 infection (PASC); however, little is known about the underlying biological factors that may direct lung recovery and the extent to which these are affected by COVID-19 severity.METHODSWe performed a prospective cohort study of individuals with persistent symptoms after acute COVID-19, collecting clinical data, pulmonary function tests, and plasma samples used for multiplex profiling of inflammatory, metabolic, angiogenic, and fibrotic factors.RESULTSSixty-one participants were enrolled across 2 academic medical centers at a median of 9 weeks (interquartile range, 6-10 weeks) after COVID-19 illness: n = 13 participants (21%) had mild COVID-19 and were not hospitalized, n = 30 participants (49%) were hospitalized but were considered noncritical, and n = 18 participants (30%) were hospitalized and in the intensive care unit (ICU). Fifty-three participants (85%) had lingering symptoms, most commonly dyspnea (69%) and cough (58%). Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and diffusing capacity for carbon monoxide (DLCO) declined as COVID-19 severity increased (P < 0.05) but these values did not correlate with respiratory symptoms. Partial least-squares discriminant analysis of plasma biomarker profiles clustered participants by past COVID-19 severity. Lipocalin-2 (LCN2), MMP-7, and HGF identified by our analysis were significantly higher in the ICU group (P < 0.05), inversely correlated with FVC and DLCO (P < 0.05), and were confirmed in a separate validation cohort (n = 53).CONCLUSIONSubjective respiratory symptoms are common after acute COVID-19 illness but do not correlate with COVID-19 severity or pulmonary function. Host response profiles reflecting neutrophil activation (LCN2), fibrosis signaling (MMP-7), and alveolar repair (HGF) track with lung impairment and may be novel therapeutic or prognostic targets.FundingNational Heart, Lung, and Blood Institute (K08HL130557 and R01HL142818), American Heart Association (Transformational Project Award), the DeLuca Foundation Award, a donation from Jack Levin to the Benign Hematology Program at Yale University, and Duke University.

The Effect of Balloon-Blowing Exercise on Postoperative Pulmonary Functions in Patients Undergoing Total Hip Arthroplasty.

General anesthesia, prolonged immobilization, and pain may adversely affect pulmonary function in patients undergoing prosthetic surgery. The aim of this study was to evaluate the effect of balloon-blowing exercises on pulmonary functions in patients undergoing total hip arthroplasty. The patients in the experimental group performed three sets of balloon-blowing exercises in the morning, at noon, and in the evening on the first to third days postoperatively. The increase in forced vital capacity (FVC) values between the control and experimental groups in the postoperative period was statistically significant (p < .001), in favor of the experimental group. The increase in forced expiratory volume during the first second (FEV1)/FVC ratio was found to be significantly higher in the experimental group than in the control group (p < .001). Patients who performed balloon-blowing exercises increased their FVC and FEV1/FVC ratio.

Survival and Lung Transplant Outcomes for Individuals With Advanced Cystic Fibrosis Lung Disease Living in the United States and Canada: An Analysis of National Registries.

BACKGROUND: Understanding how health outcomes differ for patients with advanced cystic fibrosis (CF) lung disease living in the United States compared with Canada has health policy implications. RESEARCH QUESTION: What are rates of lung transplant (LTx) and rates of death without LTx in the United States and Canada among individuals with FEV1 < 40% predicted? STUDY DESIGN AND METHODS: This was a retrospective population-based cohort study, 2005 to 2016, using the US CF Foundation, United Network for Organ Sharing, and Canadian CF registries. Individuals with CF and at least two FEV1 measurements < 40% predicted within a 5-year period, age ≥ 6 years, without prior LTx were included. Multivariable competing risk regression for time to death without LTx (LTx as a competing risk) and time to LTx (death as a competing risk) was performed. RESULTS: There were 5,899 patients (53% male) and 905 patients (54% male) with CF with FEV1 < 40% predicted living in the United States and Canada, respectively. Multivariable competing risk regression models identified an increased risk of death without LTx (hazard ratio [HR], 1.79; 95% CI, 1.52-2.1) and decreased LTx (HR, 0.66; 95% CI, 0.58-0.74) among individuals in the United States compared with Canada. More pronounced differences were seen in the patients in the United States with Medicaid/Medicare insurance compared with Canadians (multivariable HR for death without LTx, 2.24 [95% CI, 1.89-2.64]; multivariable HR for LTx, 0.54 [95% CI, 0.47-0.61]). Patients of nonwhite race were also disadvantaged (multivariable HR for death without LTx, 1.56 [95% CI, 1.32-1.84]; multivariable HR for LTx, 0.47 [95% CI, 0.36-0.62]). INTERPRETATION: There are lower rates of LTx and an increased risk of death without LTx for US patients with CF with FEV1 < 40% predicted compared with Canadian patients. Findings are more striking among US patients with CF with Medicaid/Medicare health insurance, and nonwhite patients in both countries, raising concerns about underuse of LTx among vulnerable populations.

Clinical and radiological results of surgically treated patients with adolescent idiopathic scoliosis and the effects of pulmonary rehabilitation on respiration functions.

BACKGROUND: In the present study, we aimed to evaluate the effects of pulmonary rehabilitation on respiratory functions after the surgery on the basis of early radiological findings, pain degree, function, and satisfaction scores in operated patients with adolescent idiopathic scoliosis (AIS). METHODS: Thirty patients with AIS were included in the present study, who were divided into 2 groups. Scoliosis surgery and diaphragmatic breathing and pursed lip exercises were applied in Group 1 (n = 15), whereas merely scoliosis surgery was applied in Group 2 (n = 15). Pulmonary functions, arterial blood gas analysis, Cobb and kyphosis angles, apical vertebral rotation, and apical vertebral translation were measured before and 1st and 6th months after the surgery. Using the SRS-30 test, the psychosocial statuses of the patients and their satisfaction degrees with surgery applied were measured before and after the surgery. RESULTS: Six months after the surgery, the values of Cobb and kyphosis angles and apical vertebral rotations, and apical vertebral translation of the patients were determined to be significantly ameliorated, which is consistent with the literature. Forced vital capacity (l) and forced expiratory volume in the first second (l/s) were observed to be significantly improved in both groups after the surgery (respectively, P = .001, P = .014, P = .001, P = .005). In addition, the partial pressure of oxygen (pO2) value was found to be significantly increased 6 months after the surgery compared with that before the surgery in Group 2 (P = .022). SRS-30 showed that most of the scores in Group 1 were dramatically increased; a significant difference between the groups was not recorded. CONCLUSION: Patients with AIS have been found to be satisfied with the surgery. Conversely, pulmonary rehabilitation has been shown to slightly improve the respiratory functions in the patients with AIS, 1 and 6 months after the surgery.

Improvement of Pulmonary Function in Cystic Fibrosis Patients following Endoscopic Sinus Surgery.

OBJECTIVE/HYPOTHESIS: To compare pre-and post-operative pulmonary function relative to disease severity in cystic fibrosis (CF) patients following endoscopic sinus surgery (ESS). STUDY DESIGN: Retrospective chart review. METHODS: Patients with CF who underwent ESS between January 1996 and July 2018 were identified, with subsequent study exclusions based upon surgical indications or incomplete records. CF disease severity was based upon percentage predicted of forced expiratory volume in 1 second (%FEV1) with <40% considered severe disease, 40% to 70% as moderate disease, and >70% as mild disease. The changes in %FEV1 before and after ESS were examined using multivariable mixed-effects models controlling for age, gender, genotype, medications, nutritional status, diabetes status, microbiology results, extent of surgery, and number of surgeries. RESULTS: A total of 427 surgeries were performed in 188 patients during the study period. Mean age at first ESS was 12.7 years (SD 6.0 years, range 4-38) and 54.8% were females. The effect of ESS varied by severity of lung disease. After surgery, %FEV1 increased by 8.1% (95% CI: 2.3, 13.9%) among patients with severe lung disease and by 3.0% (95% CI: 0.7, 5.2%) among patients with moderate disease. %FEV1 also increased by 7.3% (95% CI: 4.2, 10.5%) among patients with mild disease whose %FEV1 value was 70% to 80% at baseline. No improvement was observed in patients with a baseline %FEV1 >80%. CONCLUSIONS: When controlling for important confounding factors, lung function improved following ESS among CF patients with severe and moderate disease and in select patients with mild disease. This improvement was sustained at 12 months following surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1930-1938, 2021.

Preoperative resource utilization prior to minimally invasive repair of pectus excavatum.

BACKGROUND: Preoperative testing to assess the physiologic impact of pectus excavatum is sometimes ordered to meet third-party payor preauthorization requirements. This study describes the utility of physiologic testing prior to minimally invasive repair of pectus excavatum (MIRPE). METHODS: We retrospectively reviewed patients that underwent MIRPE from 1/2012-7/2016 at two academic children's hospitals. Data collected included demographics, insurance, Haller Index (HI), pulmonary function tests (PFTs) and echocardiograms (ECHO) obtained, and preauthorization denials. RESULTS: A total of 360 patients (mean age 15.7 ± 2.0 years; mean HI 4.5 ± 1.5) underwent MIRPE (Hospital 1: 189, Hospital 2: 171). Commercial insurers covered 84% of patients. Hospital 1 obtained more frequent preoperative testing (PFTs: 73% vs 6%, p < 0.0001). Overall, 72% of PFTs were normal with abnormal studies limited to mild findings. Similarly, 85% of ECHOs were normal. Third-party payors more frequently denied preauthorization for MIRPE at Hospital 2 (11% vs. 5%, p = 0.03). CONCLUSIONS: More frequent preoperative testing may decrease initial preauthorization denials for MIRPE; however, this increased utilization of resources may not be necessary as the majority of test results are normal.

Pneumothorax in Patients with Idiopathic Pleuroparenchymal Fibroelastosis: Incidence, Clinical Features, and Risk Factors.

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare form of idiopathic interstitial pneumonia that is characterized by predominantly upper lobe pleural and subpleural lung parenchymal fibrosis. Pneumothorax is one of the major respiratory complications in PPFE patients; however, its clinical features are poorly understood. OBJECTIVE: We aimed to investigate the complication of pneumothorax in patients with idiopathic PPFE. METHODS: A retrospective multicenter study involving 89 patients who had been diagnosed with idiopathic PPFE was conducted. We investigated the cumulative incidence, clinical features, and risk factors of pneumothorax after the diagnosis of idiopathic PPFE. RESULTS: Pneumothorax developed in 53 patients (59.6%) with 120 events during the observation period (41.8 ± 35.0 months). The cumulative incidence of pneumothorax was 24.8, 44.9, and 53.9% at 1, 2, and 3 years, respectively. Most events of pneumothorax were asymptomatic (n = 85; 70.8%) and small in size (n = 92; 76.7%); 30 patients (56.6%) had recurrent pneumothorax. Chest drainage was required in 23 pneumothorax events (19.2%), and a persistent air leak was observed in 13 (56.5%). Patients with pneumothorax were predominantly male and frequently had pathological diagnoses of PPFE and prior history of pneumothorax and corticosteroid use; they also had significantly poorer survival than those without pneumothorax (log-rank test; p = 0.001). Multivariate analysis revealed that a higher residual volume/total lung capacity ratio was significantly associated with the development of pneumothorax after the diagnosis. CONCLUSION: Pneumothorax is often asymptomatic and recurrent in patients with idiopathic PPFE, leading to poor outcomes in some cases.

An assessment of the correlation between robust CT-derived ventilation and pulmonary function test in a cohort with no respiratory symptoms.

OBJECTIVE: To evaluate CT-ventilation imaging (CTVI) within a well-characterized, healthy cohort with no respiratory symptoms and examine the correlation between CTVI and concurrent pulmonary function test (PFT). METHODS: CT scans and PFTs from 77 Caucasian participants in the NORM dataset (clinicaltrials.gov NCT00848406) were analyzed. CTVI was generated using the robust Integrated Jacobian Formulation (IJF) method. IJF estimated total lung capacity (TLC) was computed from CTVI. Bias-adjusted Pearson's correlation between PFT and IJF-based TLC was computed. RESULTS: IJF- and PFT-measured TLC showed a good correlation for both males and females [males: 0.657, 95% CI (0.438-0.797); females: 0.667, 95% CI (0.416-0.817)]. When adjusting for age, height, smoking, and abnormal CT scan, correlation moderated [males: 0.432, 95% CI (0.129-0.655); females: 0.540, 95% CI (0.207-0.753)]. Visual inspection of CTVI revealed participants who had functional defects, despite the fact that all participant had normal high-resolution CT scan. CONCLUSION: In this study, we demonstrate that IJF computed CTVI has good correlation with concurrent PFT in a well-validated patient cohort with no respiratory symptoms. ADVANCES IN KNOWLEDGE: IJF-computed CTVI's overall numerical robustness and consistency with PFT support its potential as a method for providing spatiotemporal assessment of high and low function areas on volumetric non-contrast CT scan.

Effects of Waterpipe Tobacco Smoking on the Spirometric Profile of University Students in Palestine: A Cross-Sectional Study.

Background: Waterpipe smoking in young individuals is increasing with limited studies addressing its respiratory health effects. The aim of the study was to determine the effect of waterpipe smoking on young adults' lung functions. Spirometric parameters were compared between waterpipe smokers and nonsmokers. Methods: A comparative cross-sectional study of university students, including males and females, was conducted. An interviewer-administered questionnaire was used to record students' characteristics. The spirometry test was performed to assess students' lung functions; we recorded the forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, peak expiratory flow (PEF), and forced expiratory flow between 25 and 75% of FVC (FEF25-75%). Results: A total of 300 apparently healthy students (150 waterpipe smokers and 150 nonsmokers) were included in the study. Waterpipe smokers showed significantly lower values in FEV1, FEV1/FVC ratio, PEF, and FEF25-75% compared to the nonsmoker group (P < 0.05 to P < 0.001). The subgroup analysis on female students (50 WP smokers and 50 nonsmokers) showed a significant decrease in FEV1/FVC ratio, PEF, and FEF25-75% parameters (P < 0.001). Conclusion: Waterpipe smoking is associated with reduced spirometric parameters in healthy young adults with relatively limited smoking years.

Experience with tocilizumab in severe COVID-19 pneumonia after 80 days of follow-up: A retrospective cohort study.

OBJECTIVES: To describe the clinical characteristics and predictors of major outcomes in patients treated with tocilizumab (TCZ) for severe COVID-19 pneumonia. PATIENTS AND METHODS: Case series of all sequential patients with severe COVID-19 pneumonia treated with TCZ at an Academic Spanish hospital (March 12 - May 2, 2020). Clinical outcomes: death, length of hospital stay. An early clinical response to TCZ (48-72 h after the administration) was assessed by variations in respiratory function markers, Brescia COVID Respiratory Severity Scale (BCRSS), inflammatory parameters, and patients' and physicians' opinion. Associations were tested by multiple logistic regression. RESULTS: From a cohort of 236 patients, 77 patients treated with TCZ were included (median age 62 years (IQR 53.0-72.0), 64.9% were males), 42.9% had Charlson index ≥3; hypertension (41.6%), obesity (34.7%), and diabetes (20.8%). Median follow-up was 83.0 days (78.0-86.5), no patient was readmitted. ICU admission was required for 42 (54.5%), invasive mechanical ventilation in 38 (49.4%) and 10 patients died (12.9% global, 23.8% at ICU admitted). After multivariate adjustment, TCZ response by BCRSS (OR 0.03 (0.01-0.68), p = 0.028), and Charlson index (OR 3.54 (1.20-10.44), p = 0.022) has been identified as independent factors associated with mortality. Median of hospital stay was 16.0 days (11.0-23.0); BCRSS, physician subjective and D-dimer response were associated with shorter hospitalization stay. CONCLUSIONS: In a Mediterranean cohort, use of tocilizumab for severe COVID-19 show 12.9% of mortality. Early TCZ-response by BCRSS and low comorbidity were associated with increased survival. Early TCZ-response was related to shorter median hospital stay.

Change in Dynamic Hyperinflation After Bronchoscopic Lung Volume Reduction in Patients with Emphysema.

BACKGROUND AND PURPOSE: In patients with severe emphysema, dynamic hyperinflation is superimposed on top of already existing static hyperinflation. Static hyperinflation reduces significantly after bronchoscopic lung volume reduction (BLVR). In this study, we investigated the effect of BLVR compared to standard of care (SoC) on dynamic hyperinflation. METHODS: Dynamic hyperinflation was induced by a manually paced tachypnea test (MPT) and was defined by change in inspiratory capacity (IC) measured before and after MPT. Static and dynamic hyperinflation measurements were performed both at baseline and 6 months after BLVR with endobronchial valves or coils (treatment group) or SoC (control group). RESULTS: Eighteen patients underwent BLVR (78% female, 57 (43-67) years, FEV1 25(18-37) %predicted, residual volume 231 (182-376) %predicted). Thirteen patients received SoC (100% female, 59 (44-74) years, FEV1 25 (19-37) %predicted, residual volume 225 (152-279) %predicted. The 6 months median change in dynamic hyperinflation in the treatment group was: + 225 ml (range - 113 to + 803) (p < 0.01) vs 0 ml (- 1067 to + 500) in the control group (p = 0.422). An increase in dynamic hyperinflation was significantly associated with a decrease in residual volume (r = - 0.439, p < 0.01). CONCLUSION: Bronchoscopic lung volume reduction increases the ability for dynamic hyperinflation in patients with severe emphysema. We propose this is a consequence of improved static hyperinflation.

Association of Neutrophil to Lymphocyte Ratio With Pulmonary Function in a 30-Year Longitudinal Study of US Veterans.

Importance: Chronic obstructive pulmonary disease (COPD) is a critical public health burden. The neutrophil to lymphocyte ratio (NLR), an inflammation biomarker, has been associated with COPD morbidity and mortality; however, its associations with lung function decline and COPD development are poorly understood. Objective: To explore the associations of NLR with lung function decline and COPD risks. Design, Setting, and Participants: This longitudinal cohort study included white male veterans in the US with more than 30 years of follow-up to investigate the associations of NLR with lung function, COPD, and hypomethylation of cg05575921, the top DNA methylation marker of lung function changes in response to tobacco smoking. This study included 7466 visits from 1549 participants, each examined up to 13 times between 1982 and 2018. A subgroup of 1411 participants without COPD at baseline were selected to analyze the association of NLR with incident COPD. Data were analyzed from September 2019 to January 2020. Exposures: The primary exposure was NLR, which was estimated using automated whole blood cell counts based on a blood sample collected at each visit. The methylation level of cg05575921 was measured in blood DNA from a subgroup of 1228 visits. Main Outcomes and Measures: The outcomes of interest were lung function, measured as forced respiratory volume in the first second (FEV1) in liters, forced vital capacity (FVC) in liters, percentage of FVC exhaled in the first second (FEV1/FVC), and maximal midexpiratory flow rate (MMEF) in liters per minute and COPD status, defined as meeting the Global Initiative for Chronic Obstructive Lung Diseases stage II (or higher) criteria. Both outcomes were measured as each visit. Results: Among 1549 included men (mean [SD] age, 68.3 [9.3] years) with 7466 visits from 1982 to 2018, a 1-unit increase in NLR was associated with statistically significant mean (SE) decreases of 0.021 (0.004) L in FEV1, 0.016 (0.005) L in FVC, 0.290% (0.005) L in FVC, 0.290% (0.065%) in FEV1/FVC, and 3.65 (0.916) L/min MMEF. Changes in NLR up to approximately 10 years were associated with corresponding longitudinal changes in lung function. Furthermore, this increase in NLR was associated with 9% higher odds of COPD (odds ratio, 1.09 [95% CI, 1.03-1.15]) for all visits and 27% higher risk of incident COPD (odds ratio, 1.07 [95% CI, 1.07-1.51]) for participants without COPD at baseline. Additionally, a 1-unit increase in NLR was associated with a mean (SE) decrease of 0.0048 (0.0021 in cg05575921 hypomethylation, which may mediate the adverse association of NLR-related inflammation on lung function. Conclusions and Relevance: These findings suggest that NLR may be a clinically relevant biomarker associated with high risk of lung function impairment and COPD alone or in combination with DNA methylation profiles.

Acute Effects of a Heat-Not-Burn Tobacco Product on Pulmonary Function.

Background and objectives: During the last decade, conventional tobacco smoking is experiencing a decline and new smoking products have been introduced. IQOS ("I-Quit-Ordinary-Smoking") is a type of "heat-not-burn" (HNB) tobacco product. The impact of IQOS on respiratory health is currently not defined. The objectives of this study were to evaluate the acute effects of IQOS on pulmonary function in non-smokers and current smokers. Materials and Methods: Fifty male healthy non-smokers and current smokers with no known co-morbidity underwent an exhaled CO measurement, oximetry (SaO2%), pulmonary function tests (flows, volumes and diffusion capacity), and a measurement of respiratory resistances with an impulse oscillometry system (IOS) before and immediately after IQOS use. Results: In the whole group of 50 participants, SaO2%, forced expiratory flow at 25% and 50% of vital capacity (FEF 25%, FEF 50%, respectively), peak expiratory flow (PEF), and diffusion lung capacity for carbon monoxide/VA (KCO) decreased significantly after IQOS use, whereas exhaled CO and airway resistance (R5 Hz, R10 Hz, r15 Hz, R20 Hz, R25 Hz, R35 Hz) increased. When the groups of smokers and non-smokers were compared, in both groups (all males, 25 smokers and 25 non-smokers), exhaled CO increased and SaO2% decreased after IQOS use (p < 0.001). In the group of non-smokers, PEF (pre 8.22 ± 2.06 vs. post 7.5 ± 2.16, p = 0.001) and FEF 25% (pre 7.6 ± 1.89 vs. 7.14 ± 2.06, p = 0.009) decreased significantly; respiratory resistances R20 Hz (pre 0.34 ± 0.1 vs. post 0.36 ± 0.09, p = 0.09) and R25 Hz (pre 0.36 ± 0.1 vs. post 0.38 ± 0.09, p = 0.08) increased almost significantly. In smokers, PEF (pre 7.69 ± 2.26 vs. post 7.12 ± 2.03, p = 0.007) and expiratory reserve volume (ERV) (pre 1.57 ± 0.76 vs. post1.23 ± 0.48, p = 0.03) decreased and R35 Hz (pre 0.36 ± 0.11 vs. post 0.39 ± 0.11, p = 0.047) increased. The differences in the changes after the use of IQOS did not differ between groups. Conclusions: IQOS had an impact on exhaled CO, SaO2%, and airways function immediately after use. Even though these changes were rather small to be considered of major clinical importance, they should raise concerns regarding the long-term safety of this product. Further research is needed for the short- and long-term effects of IQOS, especially in patients with respiratory disease.

Smoking status affects clinical characteristics and disease course of acute exacerbation of chronic obstructive pulmonary disease: A prospectively observational study.

Existing studies primarily explored chronic obstructive pulmonary disease (COPD) in smokers, whereas the clinical characteristics and the disease course of passive or nonsmokers have been rarely described. In the present study, patients hospitalized and diagnosed as acute exacerbation of COPD (AECOPD) were recruited and followed up until being discharged. Clinical and laboratory indicators were ascertained and delved into. A total of 100 patients were covered, namely, 52 active smokers, 34 passive smokers, and 14 nonsmokers. As revealed from the results here, passive or nonsmokers developed less severe dyspnea (patients with modified Medical Research Council scale (mMRC) <2, 0.0% vs. 8.8% vs. 14.3%, p < 0.05, active, passive, and nonsmokers, respectively), higher oxygenation index (206.4 ± 45.5 vs. 241.2 ± 51.1 vs. 242.4 ± 41.8 mmHg, p < 0.01), as well as lower arterial partial pressure of carbon dioxide (70.8 ± 12.7 vs. 58.85 ± 9.9 vs. 56.6 ± 6.5 mmHg, p < 0.001). Despite lower treatment intensity over these patients, amelioration of dyspnea, mitigation of cough, and elevation of oxygenation index were comparable to those of active smokers. However, in terms of patients exhibiting mMRC ≥2 and type 2 respiratory failure, amelioration of dyspnea was more common in nonsmokers as compared with passive smokers (46.4% vs. 83.3%, p < 0.05, passive and nonsmokers, respectively). In terms of patients exhibiting Global Initiative for COPD severity <3, mMRC ≥2, and type 2 respiratory failure, active smokers achieved the least mitigation of cough symptom (8.7% vs. 35.0% vs. 44.4%, p < 0.05). Similar results could be achieved after the effects of confounders were excluded, with the most prominent amelioration of dyspnea (odds ratio (OR) 3.8, 95% confidence interval (CI) 1.1-13.6, p < 0.05, as compared with active smokers) and cough (OR 3.3, 95% CI 1.0-10.7, p < 0.05) in nonsmokers, and relatively better amelioration of hypoxemia in passive smokers (oxygenation index change, 39.0 ± 34.6 vs. 51.5 ± 32.4 vs. 45.3 ± 25.4 mmHg, p < 0.05). In brief, passive or nonsmokers with AECOPD were subjected to less severe disease, and nonsmokers, especially patients with more severe disease, might achieve the optimal enhancement of clinical presentation after treatment.

Changes in the parent cystic fibrosis questionnaire-revised (CFQ-R) with respiratory symptoms in preschool children with cystic fibrosis.

INTRODUCTION: The Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory score is a validated and widely used patient-reported outcome. This study aimed to establish changes in the score with acute respiratory events in preschool children with CF and to investigate its' relationship with physiological outcomes. METHODS: The Parent CFQ-R, multiple breath washout test and spirometry were performed at six study visits over one year. The clinical status of participants, stable or symptomatic, was defined by the patient's physician. Linear regression and distribution-based statistical methods were used to examine the changes in the CFQ-R from the last stable visit and to investigate its relationship with physiological outcomes. RESULTS: There were 272 stable and 115 symptomatic visits from 78 participants. The mean CFQ-R Respiratory score did not change between consecutive stable visits (-0.73, SD 20.4). The mean (SD) score deteriorated by 15.5 (20.7) points between stable and symptomatic visits and improved by 14.8 (20.1) points between symptomatic and stable follow-up visits. When a clinically important change is defined as 0.5SD change (10-points), the positive predictive value (PPV) was 45% and the negative predictive value (NPV) was 84%. For visits with a 10-point worsening in the CFQ-R Respiratory score and a 15% increase in LCI, the PPV was better (81%) than using either measure alone. CONCLUSION: The CFQ-R Respiratory score is responsive to acute respiratory events in preschool children with CF and its utility to monitor individual patients is improved when combined with LCI.

Health-related quality-of-life in children with cystic fibrosis aged 5-years and associations with health outcomes.

BACKGROUND: The impact of early cystic fibrosis (CF) on health-related quality-of-life (HRQOL) in preschool children is poorly characterised, and data on relationships between HRQOL and health outcomes in young children with CF are limited. We aimed to characterise and compare parent-proxy and child-reported HRQOL and evaluate relationships with clinical outcomes at age 5-years. METHODS: Subjects were participating in the multi-centre Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) trial investigating BAL-directed versus standard CF therapy. Children aged 5-years and their parents rated HRQOL using the Pediatric Quality of Life Inventory (PedsQL™) and Cystic Fibrosis Questionnaire-Revised (CFQ-R) questionnaires. RESULTS: PedsQL and CFQ-R questionnaires were completed by 141 primary caregivers and 135 and 130 children, respectively. There were no differences in HRQOL between children randomised to BAL-directed versus standard CF therapy. Children with CF rated worse HRQOL than healthy children and there was poor parent-child concordance across HRQOL domains. Nutritional status, CF-CT scan score, forced expiratory volume in 1-second (FEV1), and pulmonary exacerbations correlated with HRQOL at age 5-years. FEV1 z-scores positively correlated with parent-proxy HRQOL in CFQ-R Respiratory (p = 0.018), Physical (<0.001), Emotional (p = 0.007) subscales and PedsQL Total-score (p = 0.021), Physical (p = 0.019) domains. Pulmonary exacerbation rates were inversely associated with parent-proxy CFQ-R Respiratory (p = 0.004), Physical (p = 0.022), PedsQL Total (p = 0.009) and Physical (p = 0.009) scores. CONCLUSION: Parent-reported HRQOL is a meaningful clinical endpoint to evaluate interventions in young children. Parent and child HRQOL reports provide different, complementary information. A preschool version of the CFQ-R is needed to assess relationships between HRQOL and clinical outcomes in young children.