Prevalence of pulmonary embolism in patients with obstructive sleep apnea and chronic obstructive pulmonary disease: The overlap syndrome

ObjectiveGrowing evidence indicates that both obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) may be closely associated with the prevalence of pulmonary embolism (PE). However, the relationship of overlap syndrome (OS) (coexistence of OSA and COPD) with PE is unclear. The purpose of this study was to investigate whether OS were associated with increased PE prevalence.MethodsWe performed a retrospective chart review of patients who underwent sleep study at Beijing An Zhen Hospital from 2011 to 2014. The association of OS with PE prevalence was estimated by using logistic regression models.ResultsIn contrast to control patients (neither OSA nor COPD), those subjects with OS had higher odds of PE (OR9.61; 95%CI 4.02–21.31, p < 0.001) with significance persisting after adjusting for covariates (OR 5.66; 95%CI 1.80–16.18, p = 0.004). Meanwhile, patients with OS compared with those with isolated OSA also had significantly higher odds of PE in univariate (OR 4.79; 95%CI 2.04–10.33, p = 0.0007) and adjusted models (OR 3.89; 95%CI 1.27–10.68, p = 0.019). In subgroup analysis, patients with OS had higher odds of PE than control group among male subjects (OR 8.12, 95%CI1.86–31.87, p = 0.007) and patients ≥ 58years (OR 5.50, 95%CI 1.51–18.14, p = 0.012) in multivariable models. Percentage of total sleep time with saturation lower than 90% (T90) ≥ 2.6% was significantly associated with prevalence of PE (OR 4.72, 95%CI1.34–19.83, p = 0.015) in subgroup of patients older than 58.ConclusionsOS is independently associated with PE prevalence. Longitudinal studies are needed to better understand the relationship with incident PE.     

Cellular senescence—an aging hallmark in chronic obstructive pulmonary disease pathogenesis

Chronic obstructive pulmonary disease (COPD),¹ a representative aging-related pulmonary disorder, is mainly caused by cigarette smoke (CS) exposure. Age is one of the most important risk factors for COPD development, and increased cellular senescence in tissues and organs is a component of aging. CS exposure can induce cellular senescence, as characterized by irreversible growth arrest and aberrant cytokine secretion of the senescence-associated secretory phenotype; thus, accumulation of senescent cells is widely implicated in COPD pathogenesis. CS-induced oxidative modifications to cellular components may be causally linked to accelerated cellular senescence, especially during accumulation of damaged macromolecules. Autophagy is a conserved mechanism whereby cytoplasmic components are sent for lysosomal degradation to maintain proteostasis. Autophagy diminishes with age, and loss of proteostasis is one of the hallmarks of aging. We have reported the involvement of insufficient autophagy in regulating CS-induced cellular senescence with respect to COPD pathogenesis. However, the role of autophagy in COPD pathogenesis can vary based on levels of cell stress and type of selective autophagy because excessive activation of autophagy can be responsible for inducing regulated cell death. Senotherapies targeting cellular senescence may be effective COPD treatments. Autophagy activation could be a promising sonotherapeutic approach, but the optimal modality of autophagy activation should be examined in future studies.     

Hydrogen sulfide as a novel biomarker of asthma and chronic obstructive pulmonary disease

Hydrogen sulfide (H₂S) has recently been recognised as the third important gas-signalling molecule, besides nitric oxide and carbon monoxide. H₂S has been reported to be produced by many cell types in mammalian tissues and organs throughout the actions of H₂S-generating enzymes or redox reactions between the oxidation of glucose and element of sulfur. Although the pathological role of H₂S has not yet been fully elucidated, accumulative data suggest that H₂S may have biphasic effects. Briefly, it mainly has anti-inflammatory and antioxidant roles, although it can also have pro-inflammatory effects under certain conditions where rapid release of H₂S in tissues occur, such as sepsis. To date, there have been several clinical studies published on H₂S in respiratory disorders, including asthma and chronic obstructive pulmonary disease (COPD). According to previous studies, H₂S is detectable in serum, sputum, and exhaled breath, although a gold standard method for detection has not yet been established. In asthma and COPD, H₂S levels in serum and sputum can vary depending on the underlying conditions such as an acute exacerbation. Furthermore, sputum H₂S in particular correlates with sputum neutrophils and the degree of airflow limitation, indicating that H₂S has potential as a novel promising biomarker for neutrophilic airway inflammation for predicting current control state as well as future risks of asthma. In the future, concurrent measures of H₂S with conventional inflammatory biomarkers (fractional exhaled nitric oxide, eosinophils etc) may provide more useful information regarding the identification of inflammatory phenotypes of asthma and COPD for personalised treatment.     

Exhaled nitric oxide: A biomarker for chronic obstructive pulmonary disease

The fractional concentration of exhaled nitric oxide (FeNO) is recognized as a biomarker of type 2 inflammation in asthma, which is related to airway eosinophilia. We conducted a prospective observational study in a cohort of Japanese patients with chronic obstructive pulmonary disease (COPD) to evaluate the relationship between FeNO and clinical features and patient outcomes over a 3-year period. Participants were categorized into two groups based on FeNO levels (high and low), and the clinical features and outcomes were compared between the groups. Patients with high FeNO levels showed features of asthma and eosinophilic inflammation compared to those with low levels. However, high FeNO levels were not associated with worse outcomes (exacerbations, hospital admissions, all-cause and disease-specific mortality) compared to low levels. These results provide evidence that baseline FeNO is related to eosinophilic inflammation; however, is not a predictor of future exacerbations or prognosis in patients with stable COPD.     

Blood eosinophil count variability in chronic obstructive pulmonary disease and severe asthma

BackgroundBlood eosinophils are essential biomarkers that vary substantially over time in patients with COPD and asthma. However, no study has identified the changes and effects in the changes of the blood eosinophil counts over time in both diseases. This study aimed to demonstrate blood eosinophil variability in patients with COPD and severe asthma based on these backgrounds.MethodsA total of 172 patients with COPD from the Hokkaido COPD cohort study and 96 patients with severe asthma from the Hokkaido Severe Asthma Cohort Study, whose blood eosinophil counts were measured annually over a 3-year period, were analyzed. The factors contributing to consistently high or low blood eosinophil counts were examined in each cohort. The stability of the eosinophil classification (<150, 150–299, ≥300 cells/μL) was compared based on the number of asthma-like features in patients with COPD and the smoking status in patients with severe asthma.ResultsAmong all the patients, the most stable range of baseline blood eosinophil counts differed between the two diseases, with <150 cells/μL in COPD and ≥300 cells/μL in severe asthma. In COPD, the number of asthma-like features (bronchodilator reversibility, blood eosinophilia, and atopy) affects the blood eosinophil count variation patterns. In severe asthma, smoking status did not affect the blood eosinophil count variation patterns.ConclusionsWe identified variations in the blood eosinophil counts and their contributing factors in patients with COPD and severe asthma.     

Treatment efficacy of LAMA versus placebo for stable chronic obstructive pulmonary disease: A systematic review and meta-analysis

BackgroundFour long-acting muscarinic antagonists (LAMAs), tiotropium, glycopyrronium, aclidinium, and umeclidinium, are currently available for the treatment of stable chronic obstructive pulmonary disease (COPD). However, no integrated analysis has sought to determine the effectiveness of these LAMAs. Thus, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of LAMA versus placebo in patients with stable COPD.MethodsA literature search of relevant randomized control trials that administered LAMA to stable COPD patients was conducted, and the exacerbations, quality of life (QoL), dyspnea score, lung function, and adverse event of patients were evaluated.ResultsA total of 33 studies were included in this meta-analysis. LAMA significantly decreased the frequency of exacerbations compared to the placebo (OR 0.75; 95% CI 0.66 to 0.85; P < 0.001). The mean changes in the St George's Respiratory Questionnaire score (mean difference, ?3.61; 95% CI, ?4.27 to ?2.95; P < 0.00001), transitional dyspnea index score (mean difference 1.00; 95% CI 0.83 to 1.17; P < 0.00001), and trough FEV₁ (mean difference 0.12; 95% CI 0.11 to 0.13; P < 0.0001) indicated significantly greater improvement in the LAMA group than the placebo group. The number of withdrawals due to adverse events in the LAMA group was significantly fewer than that in the placebo group (OR -0.02; 95% CI -0.03 to ?0.01; P = 0.002).ConclusionLAMA is superior to placebo due to lower frequency of exacerbations and adverse events, as well as higher trough FEV₁, QoL, and dyspnea score for stable COPD.     

Quantitative computed tomography-based evaluation of skeletal muscle and presence of sarcopenia in patients with chronic obstructive pulmonary disease

Sarcopenia, or age-related muscle loss, is a common comorbidity in patients with chronic obstructive pulmonary disease (COPD) with multiple contributing factors. We hypothesized that the presence of sarcopenia can be estimated using quantitative computed tomography-based parameters in patients with COPD. We retrospectively evaluated 38 elderly (≥65 years) men with COPD for pooled data, including hand grip strength and gait speed. Sarcopenia was diagnosed based on the updated 2019 criteria set by the Asian Working Group for Sarcopenia. Cross-sectional area of the erector spinae muscle (ESM) and pectoralis muscle (PM) were quantitatively evaluated and adjusted by height (ESM-I, and PM-I). Sarcopenia was diagnosed in 11 (29%) patients. The mean ESM-I and PM-I were 11.0 and 9.5 cm²/m², respectively, and significantly correlated with height-adjusted appendicular skeletal muscle mass. The optimal cutoff ESM-I for the presence of sarcopenia was 9.41 cm²/m². ESM loss helped estimate sarcopenia in patients with COPD.     

Correlation of 4-meter gait speed with clinical indicators of chronic obstructive pulmonary disease

BackgroundMeasuring daily physical activity and exercise capacity is recommended in the routine care of patients with chronic obstructive pulmonary disease (COPD). The 4-m gait speed (4mGS) is simple and effective in stratifying patients according to exercise performance, dyspnea, health status, and prognosis. We assessed the reliability of the 4mGS as a clinical marker by examining its association with established clinical indicators among hospitalized patients with COPD.MethodsThis retrospective study included 78 patients hospitalized with COPD (mean age: 76.3 ± 0.9 years; males, n = 69) between January 2016 and June 2018 who were assessed using the 4mGS and divided into slow (<0.8 m/s) and normal (≥0.8 m/s) 4mGS groups. Clinical characteristics were compared, including death during the observation period, time to first exacerbation, and long-term oxygen therapy requirement.ResultsThere were strong relationships between 4mGS performance, the 6-min walk test (R = 0.70; p < 0.0001), and the modified Medical Research Council dyspnea scale (R = 0.68; p < 0.0001) among the 78 patients. The slow 4mGS group had a higher frequency of death during the observation period (p = 0.0095) and a greater requirement for long-term oxygen therapy (p = 0.0063). The 4mGS correlated with inspiratory capacity (IC) and IC/total lung capacity ratios, which are respiratory failure indicators.ConclusionsThe 4mGS is a simple and easy method of assessing the physical condition as well as estimating the prognosis of patients with COPD, and may serve as a useful marker in home medical treatment or clinical settings.     

Association between low mean corpuscular hemoglobin and prognosis in patients with exacerbation of chronic obstructive pulmonary disease

BackgroundSeveral studies have demonstrated the association between mean corpuscular hemoglobin concentration (MCHC), a hematological index used for the assessment of anemia, and the prognosis of patients with heart disease. While the red cell distribution width (RDW) is known to be related to the prognosis of patients with chronic obstructive pulmonary disease (COPD), few studies have focused on the association between the MCHC and COPD. Therefore, we examined the association between the MCHC and prognosis in patients with exacerbation of COPD.MethodsWe examined the association between the 30-day mortality and clinical findings in patients with COPD exacerbation who were hospitalized between October 2008 and December 2018.ResultsWe enrolled 195 patients with COPD exacerbation (average age: 76.4 years; 181 men, 14 women). The MCHC was significantly lower, while the RDW was significantly higher in the 27 patients (13.8%) who died during the 30-day observation period compared to those in the patients who survived. Multivariate logistic regression analysis revealed that the MCHC was independently associated with 30-day mortality. The area under the curve calculated from the MCHC obtained from peripheral blood was 0.688 and the cutoff value was 31.6 g/dL, with a sensitivity of 0.593 and specificity of 0.810 (p = 0.0001).ConclusionThe MCHC might be a valuable biomarker for evaluating the prognosis of patients with COPD exacerbation.     

Two cases of chronic obstructive pulmonary disease evaluated by dynamic-ventilatory digital radiography for pulmonary function and assessment of treatment efficacy

Spirometry is a crucial test used in the diagnosis and monitoring of patients with chronic obstructive pulmonary disease (COPD). Severe acute respiratory syndrome coronavirus 2 pandemic has posed numerous challenges in performing spirometry. Dynamic-ventilatory digital radiography (DR) provides sequential chest radiography images during respiration with lower doses of radiation than conventional X-ray fluoroscopy and computed tomography. Recent studies revealed that parameters obtained from dynamic DR are promising for evaluating pulmonary function of COPD patients. We report two cases of COPD evaluated by dynamic-ventilatory DR for pulmonary function and treatment efficacy and discuss the potential of dynamic DR for evaluating COPD therapy.     

Differences in the spectrum of respiratory viruses and detection of human rhinovirus C in exacerbations of adult asthma and chronic obstructive pulmonary disease

BackgroundViral respiratory infections are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and asthma. We conducted a multicenter prospective study to determine the differences in the spectrum of viruses between adults with asthma exacerbations and AECOPD and assessed the prevalence and impact of human rhinovirus (HRV)-C in adults, which is more pathogenic in children with asthma than other HRV species.MethodsNasopharyngeal and serum samples and clinical information were collected from 64 outpatients with adult asthma exacerbations and 44 outpatients with AECOPD between April 2018 and March 2020. Viral pathogens and HRV strains were identified from nasal samples by multiplex PCR and VP4/VP2 nested PCR.ResultsViral pathogens were identified in 31 patients with asthma exacerbations (48.4%) and 17 patients with AECOPD (38.6%). The most commonly detected viruses were HRV/enterovirus followed by human metapneumovirus (hMPV) in patients with asthma exacerbations, and hMPV followed by parainfluenza virus in patients with AECOPD. HRV-C was the HRV species most commonly associated with both asthma exacerbations and AECOPD. Clinical characteristics, baseline lung function, serum inflammatory chemokines, hospitalization, and systemic steroid use did not differ between HRV-C-positive patients and those positive for other HRV species.ConclusionsExacerbation-associated spectrum of viruses differed between adults with asthma exacerbations and AECOPD. HRV-C was the HRV species most often observed in adult asthma exacerbations and AECOPD, although it did not worsen patients’ clinical outcomes relative to those of patients with other HRVs. Underlying disease-specific factors may be responsible for susceptibility to respiratory viruses.Trial registrationUMIN-CTR UMIN000031934.     

Increased LHX9 expression in alveolar epithelial type 2 cells of patients with chronic obstructive pulmonary disease

BackgroundAlveolar epithelial type 2 (AT2) cells serve as stem cells in alveolar epithelium and are assumed to lose their stem cell function in the lungs of chronic obstructive pulmonary disease (COPD). Although we previously reported that LHX9 mRNA expression was up-regulated in AT2 cells of COPD lung tissues, it is yet to be elucidated how LHX9 is associated with the vulnerability of AT2 cells in COPD.MethodsAT2 cells were isolated from lung tissues of 10 non-COPD subjects and 11 COPD patients. LHX9 mRNA expression was determined by quantitative RT-PCR. To identify up-stream molecules, an alveolar epithelial cell line A549 was exposed to pro-inflammatory cytokines in vitro. siRNA-mediated Lhx9 knockdown was performed to determine how Lhx9 affected the cellular viability and the cell-division cycle.ResultsLHX9 mRNA expression was increased in AT2 cells from COPD lung tissues, compared to those from non-COPD tissues. The airflow obstruction was independently correlated with the increase in LHX9 expression. Among several pro-inflammatory cytokines, interferon-γ was a strong inducer of LHX9 expression in A549 cells. Lhx9 was involved in the increased susceptibility to serum starvation-induced death of A549 cells.ConclusionsOur data suggest that IFN-γ predominantly increases the LHX9 expression which enhances the susceptibility to cell death. Considering the independent association of the increased LHX9 expression in AT2 cells with airflow obstruction, the IFN-γ-Lhx9 axis might contribute to the vulnerability of AT2 cells in the lungs of COPD patients.     

Impact of post-capillary pulmonary hypertension on mortality in interstitial lung disease

BackgroundPulmonary hypertension (PH) influences mortality in patients with interstitial lung disease (ILD). Almost all studies on patients with ILD, have focused on the clinical impact of pre-capillary PH on survival. Therefore, little is known about the influence of post-capillary PH. We aimed to assess the prevalence of post-capillary PH and its clinical impact on survival in patients with ILD, followed by comparison with pre-capillary PH.MethodsThis retrospective study enrolled 1152 patients with ILD who were diagnosed with PH using right heart catheterization between May 2007 and December 2015. We analyzed the demographics and composite outcomes (defined as death from any cause or lung transplantation) of patients with post-capillary PH and compared them with patients with pre-capillary PH.ResultsThirty-two (20%) of the 157 patients with ILD-PH were diagnosed with post-capillary PH. Patients with post-capillary PH had significantly lower modified Medical Research Council scores, higher diffusion capacity for carbon monoxide, higher resting PaO₂, lower pulmonary vascular resistance (PVR), and higher lowest oxygen saturation during the 6-min walk test compared to those with pre-capillary PH. Cardiovascular diseases were associated with a higher risk of mortality in patients with post-capillary PH. Multivariate Cox proportional hazards analysis demonstrated no significant difference between the composite outcomes in pre-capillary and post-capillary PH, while PVR and the ILD Gender-Age-Physiology Index were significantly associated with the composite outcome.ConclusionsWe found that approximately one-fifth of patients with ILD-PH were diagnosed with post-capillary PH, and that PVR and not post-capillary PH was associated with mortality.     

The efficacy of mass screening for chronic obstructive pulmonary disease using screening questionnaires in a medical health check-up population

BackgroundChronic obstructive pulmonary disease (COPD) is a preventable and treatable disease, highlighting the need for efficient screening strategies to identify patients with COPD. However, there is little evidence regarding the efficacy of mass screening for COPD, and no epidemiological studies on COPD have been conducted in the Shikoku region of Japan.MethodsIn this cross-sectional study, we originally investigated the efficacy of mass screening for COPD among community residents in the aforementioned region using two COPD screening questionnaires.ResultsFrom July 2018 through January 2019, 688 participants were enrolled. COPD was diagnosed using the Global Initiative for the Chronic Obstructive Lung Disease criteria. Twenty-one patients were newly diagnosed with COPD and 19 (90.5%) had early stages COPD. The prevalence of COPD in this study was 3.1%. The COPD Population Screener (COPD-PS) questionnaire and the International Primary Care Airways Guidelines (IPAG) questionnaire had extremely high negative predictive values in discriminating participants with COPD from those without. The scores of both questionnaires were correlated with spirometric tests and with each other. The COPD-PS questionnaire had significantly better specificity and area under the receiver operating characteristic curve value than the IPAG questionnaire. Moreover, only the COPD-PS questionnaire was identified as an independent factor for predicting COPD diagnosis in the multivariate analysis.Conclusions: Mass screening for COPD using screening questionnaires, particularly the COPD-PS questionnaire, might be useful to identify the early stages of COPD in a medical health check-up population.     

Two cases of chronic obstructive pulmonary disease with undetectable diffusing capacity for carbon monoxide

Pulmonary diffusing capacity for carbon monoxide (DL_CO) is a valuable pulmonary function test to evaluate the gas exchange capacity of the lungs. Generally, DL_CO values are significantly lower in patients with chronic obstructive pulmonary disease (COPD), particularly in those with a predominantly emphysema phenotype. However, it is extremely rare that DL_CO values cannot be obtained for reasons other than technical errors. Herein, we report two patients with COPD in whom DL_CO values were undetectable without prolonging the breath-holding time for the test. We discuss possible mechanisms for these peculiar findings.     

Efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler delivered using co-suspension delivery technology in Japanese patients with moderate-to-very severe chronic obstructive pulmonary disease

BackgroundPINNACLE-4 evaluated the efficacy and safety of the long-acting muscarinic antagonist/long-acting β₂-agonist fixed-dose combination glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) in patients from Asia, Europe, and the USA with moderate-to-very severe chronic obstructive pulmonary disease (COPD). This pre-specified analysis included Japanese patients in PINNACLE-4.MethodsIn this double-blind randomized study (NCT02343458), patients received GFF MDI (18/9.6 μg), glycopyrrolate (GP) MDI (18 μg), formoterol fumarate (FF) MDI (9.6 μg), or placebo MDI twice daily for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV₁) over Weeks 12–24. Secondary lung function endpoints, patient-reported outcomes, and safety were assessed. The Japanese subpopulation (n = 150) analyses were exploratory.ResultsGFF MDI improved change from baseline in morning pre-dose trough FEV₁ over Weeks 12–24 versus GP MDI, FF MDI, and placebo MDI (least squares mean [LSM] differences [95% confidence interval]: 69 [8–131], 60 [–1 to 121], and 275 [180–370] mL, respectively). GFF MDI numerically improved Transition Dyspnea Index focal score and change from baseline in St George's Respiratory Questionnaire total score versus placebo MDI (LSM differences 0.19 and ?3.78, respectively). Treatment-related adverse events occurred in ≤4.5% of patients in any treatment group.ConclusionsGFF MDI improved lung function versus monocomponents and placebo MDI in the Japan subpopulation of PINNACLE-4. The efficacy and safety results were generally consistent with those of the global study population, supporting the use of GFF MDI in Japanese patients with moderate-to-very severe COPD.     

Comparison of the chest computed tomography findings between patients with pulmonary tuberculosis and those with Mycobacterium avium complex lung disease

BackgroundSince the computed tomography (CT) findings of nontuberculous mycobacterial lung disease are similar to those of pulmonary tuberculosis (PTB), we often have difficulty differentiating the two. In this study, we compared the differences in chest CT findings and their locations between cases of PTB and Mycobacterium avium complex lung disease (MACLD).MethodsThe subjects were 100 MACLD patients and 42 PTB patients treated at our hospital from May 2005 to August 2015. The CT findings were retrospectively evaluated.ResultsPTB more frequently showed lung shadows with calcification inside the lesion, calcification of the mediastinal/hilar lymph node, and pleural effusion on CT than MACLD, while extensive bronchiectasis and granular/large shadows connected to bronchiectasis were more frequently observed with MACLD than PTB. For cavitary lesions, the thinnest part of the cavity wall with MACLD was thinner than that with PTB. Granular shadows, large shadows, and bronchiectasis were typically distributed to the right upper lobe and left upper division in PTB cases vs. the right intermediate lobe and left lingula in MACLD.ConclusionsChest CT findings would therefore be useful for distinguishing PTB and MACLD when typical findings are observed.     

Bronchoscopy for the diagnosis of nontuberculous mycobacterial pulmonary disease: Specificity and diagnostic yield in a retrospective cohort study

BackgroundBronchoscopy is a recognized method for obtaining specimens for the diagnosis of nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its diagnostic properties remain to be elucidated. The aim of this study was to determine the specificity of bronchoscopy for the diagnosis of NTM-PD, and to examine the diagnostic yield of bronchoscopy for detecting nontuberculous mycobacteria (NTM) when patients cannot expectorate sputum with NTM.MethodsThis retrospective cohort study included 2657 patients who underwent bronchoscopy and mycobacterial culture between January 2004 and June 2018 in a tertiary care center in Tokyo, Japan. To examine the specificity of bronchoscopy, the first cohort comprised patients who underwent bronchoscopy for the diagnosis of lung cancer and mycobacterial culture. To investigate the diagnostic yield, patients with nodular bronchiectasis who underwent bronchoscopy for the diagnosis of NTM-PD were enrolled into the second cohort.ResultsIn total, 919 patients were diagnosed with lung cancer, 19 patients showed positive culture for NTM, and 14 patients showed findings for NTM-PD. Accordingly, the specificity was calculated as 900/905 (99.4%). In addition, NTM-PD was suspected before bronchoscopy in 199 patients; the diagnostic yield was 105/199 (52.8%). Four factors were associated with NTM-PD: upper lobe examination, absence of specific bacteria, absence of connective tissue disease, and a higher total computed tomography score.ConclusionsBronchoscopy has a high specificity for the diagnosis of NTM-PD. In addition, even when NTM is undetected in sputum, bronchoscopy may detect mycobacteria in approximately half of the patients suspected of having NTM-PD.     

Clinical significance and safety of combined treatment with chemotherapy and pulmonary rehabilitation regarding health-related quality of life and physical function in nontuberculous mycobacterial pulmonary disease

BackgroundIn the treatment of patients with nontuberculous mycobacterial pulmonary disease (NTM-PD), pulmonary rehabilitation (PR) has been recommended as a non-pharmacological therapy. However, no study has validated the combination of chemotherapy and PR in this context. This study investigated the effect of chemotherapy and supervised PR on health-related quality of life (HRQoL) and physical function in NTM-PD patients.MethodsThis prospective cohort study included patients diagnosed with NTM-PD who had a planned hospitalization of at least 3 weeks for chemotherapy and PR. HRQoL (Leicester Cough Questionnaire [LCQ] and chronic obstructive pulmonary disease assessment test [CAT]), physical function (incremental shuttle walk distance [ISWD], quadriceps force), and C-reactive protein levels were assessed before and after treatment, and the corresponding data were analyzed in conjunction with clinical data. The adverse events of PR were also investigated.ResultsForty-two patients who met the study criteria were included in the analysis. After treatment, all LCQ item scores, total CAT score and sub-item scores related to respiratory symptoms, ISWD, quadriceps force, and C-reactive protein levels were found to have improved significantly. In the chronic cough with excessive sputum production (CCS) group, the proportions of responders who showed improvements in LCQ and CAT scores and ISWD greater than the corresponding minimal clinically important difference were significantly greater than those in the non-CCS group. No PR-related adverse events were reported.ConclusionsCombined treatment with chemotherapy and PR may improve HRQoL and physical function, and supervised PR can be provided safely.     

The safety and efficacy of durvalumab consolidation therapy in the management of patients with stage III non-small-cell lung cancer and preexisting interstitial lung disease

BackgroundSome lung cancer patients have preexisting interstitial lung disease (ILD), which is considered a risk factor for lung cancer treatment. This study investigated the safety and efficacy of durvalumab consolidation therapy for patients with stage III non-small-cell lung cancer (NSCLC) and preexisting ILD.MethodsFifty consecutive patients who were judged to be tolerable to concurrent chemoradiotherapy (CCRT) for stage III NSCLC were enrolled. Differences in the incidence rate of radiation pneumonitis (RP) and progression-free survival (PFS) were assessed in patients with or without ILD of which CT showed non-usual interstitial pneumonia pattern between the durvalumab consolidation group and chemotherapy (combination of carboplatin and paclitaxel [CP]) consolidation group.ResultsThe incidence of RP was higher in patients with preexisting ILD (40% and 20% in the durvalumab and CP groups, respectively) than in those without ILD (26% and 8% in the durvalumab and CP groups, respectively). Univariate analysis showed that durvalumab therapy tended to increase the incidence of RP; however, preexisting ILD did not significantly increase the incidence of RP. The condition of all patients who developed RP improved with the administration of oral prednisolone. Among patients without ILD, the median PFS was 17 and 16 months in the durvalumab and CP groups, respectively. Among patients with preexisting ILD, median PFS was not achieved in the durvalumab group and was 8 months in the CP group.ConclusionsAlthough durvalumab consolidation therapy tended to increase the incidence of RP, it might be tolerable in stage III NSCLC patients with preexisting ILD.