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BACKGROUND: Continuous positive airway pressure (CPAP) adherence may vary based on the study design and country. OBJECTIVES: To investigate long-term CPAP adherence and elucidate associated factors. METHODS: A multicenter retrospective observational cohort study was conducted over two years. The study included patients diagnosed with obstructive sleep apnea who were prescribed CPAP (n = 1261). Adherence was assessed for 90 days and 365 days. Centers for Medicare and Medicaid Services (CMS) criteria (≥4 h/night on ≥70 % of nights) and research adherence criteria (≥4 h/night during the observational period) were used. Factors influencing CPAP adherence (CMS criteria) during 90 and 365 days were also evaluated. Continuous variables were categorized into low, middle, and high classes, and logistic regression analysis with interaction was performed. RESULTS: CPAP adherence to CMS criteria for 90 and 365 days was 45.6 % and 44.7 %, respectively, whereas adherence to research criteria was 57.0 % and 54.1 %, respectively. Middle age, high age, and high apnea ratio independently increased CPAP adherence. Conversely, a high rapid eye movement apnea-hypopnea index ratio decreased CPAP adherence. Although high body mass index (BMI) had no independent effect on adherence, its interaction with high 3 % oxygen desaturation index increased 90-day CPAP adherence. However, high BMI decreased 90-day CPAP adherence in males. The interaction between middle age and high BMI was associated with decreased CPAP adherence over 365 days. CONCLUSIONS: Adherence to CPAP in real-world settings is modest. Various factors influence CPAP adherence. BMI may exert varied effects on CPAP adherence depending on the accompanying factors.
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BACKGROUND: Japanese guidelines recommend triple inhaled corticosteroid (ICS)/long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) and no concurrent asthma diagnosis who experience frequent exacerbations and have blood eosinophil (EOS) count ≥ 300 cells/mm3, and in patients with COPD and asthma with continuing/worsening symptoms despite receiving dual ICS/LABA therapy. These post-hoc analyses of the KRONOS study in patients with COPD and without an asthma diagnosis, examine the effects of fixed-dose triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual therapies on lung function and exacerbations based on blood EOS count - focusing on blood EOS count 100 to < 300 cells/mm3 - as a function of exacerbation history and COPD severity. METHODS: In KRONOS, patients were randomized to receive treatments that included BGF 320/14.4/10 µg, glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 µg, or budesonide/formoterol fumarate dihydrate (BFF) 320/10 µg via metered dose inhaler (two inhalations twice-daily for 24 weeks). These post-hoc analyses assessed changes from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over 12-24 weeks and moderate or severe COPD exacerbations rates over 24 weeks. The KRONOS study was not prospectively powered for these subgroup analyses. RESULTS: Among patients with blood EOS count 100 to < 300 cells/mm3, least squares mean treatment differences for lung function improvement favored BGF over BFF in patients without an exacerbation history in the past year and in patients with moderate and severe COPD, with observed differences ranging from 62 ml to 73 ml across populations. In this same blood EOS population, moderate or severe exacerbation rates were reduced for BGF relative to GFF by 56% in patients without an exacerbation history in the past year, by 47% in patients with moderate COPD, and by 50% in patients with severe COPD. CONCLUSIONS: These post-hoc analyses of patients with moderate-to-very severe COPD from the KRONOS study seem to indicate clinicians may want to consider a step-up to triple therapy in patients with persistent/worsening symptoms with blood EOS count > 100 cells/mm3, even if disease severity is moderate and there is no recent history of exacerbations. TRIAL REGISTRATION: ClinicalTrials.gov registry number NCT02497001 (registration date, 13 July 2015).
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Broncodilatadores , Budesonida , Eosinófilos , Fumarato de Formoterol , Glicopirrolato , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Glicopirrolato/administração & dosagem , Feminino , Idoso , Pessoa de Meia-Idade , Broncodilatadores/administração & dosagem , Budesonida/administração & dosagem , Eosinófilos/efeitos dos fármacos , Fumarato de Formoterol/administração & dosagem , Método Duplo-Cego , Progressão da Doença , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Administração por Inalação , Resultado do Tratamento , Antagonistas Muscarínicos/administração & dosagem , Volume Expiratório Forçado/efeitos dos fármacos , Volume Expiratório Forçado/fisiologiaRESUMO
OBJECTIVE: Continuous positive airway pressure (CPAP) is the standard treatment for obstructive sleep apnea (OSA). Unsatisfactory adherence to CPAP is an important clinical issue to resolve. Cluster analysis is a powerful tool to distinguish subgroups in a multidimensional fashion. This study aimed to investigate the use of cluster analysis for predicting CPAP adherence using clinical polysomnographic (PSG) parameters and patient characteristics. PATIENTS/METHODS: Participants of this multicenter observational study were 1133 patients with OSA who were newly diagnosed and implemented CPAP. Ward's method of cluster analysis was applied to in-laboratory diagnostic PSG parameters and patient characteristics. CPAP adherence was assessed during 90- and 365-day periods after CPAP initiation in each cluster. We adopted the Centers for Medicare and Medicaid Services criterion for CPAP adherence, i.e., CPAP use ≥4 h per night for 70 % or more of the observation period. Logistic regression analysis was performed to stratify clusters according to CPAP adherence. RESULTS: Five clusters were identified through cluster analysis. Clustering was significantly associated with CPAP adherence at 90- and 365-day periods after CPAP initiation. Logistic regression revealed that the cluster with features including apnea predominant sleep-disordered breathing, high apnea-hypopnea index, and relatively older age demonstrated the highest CPAP adherence. CONCLUSION: Cluster analysis revealed hidden connections using patient characteristics and PSG parameters to successfully identify patients more likely to adhere to CPAP for 90 days and up to 365 days. When prescribing CPAP, it is possible to identify patients with OSA who are more likely to be non-adherent.
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Pressão Positiva Contínua nas Vias Aéreas , Cooperação do Paciente , Polissonografia , Apneia Obstrutiva do Sono , Humanos , Pressão Positiva Contínua nas Vias Aéreas/métodos , Masculino , Feminino , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/diagnóstico , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Análise por Conglomerados , IdosoRESUMO
A 72-year-old man with productive cough and wheezing was referred to our institution for a growing mass shadow and central bronchiectasis in the right lower lobe on computed tomography. Based on the symptoms, elevated Aspergillus-specific immunoglobulin E levels, and radiological findings, allergic bronchopulmonary mycosis (ABPM) was suspected according to the Japanese clinical diagnostic criteria. The patient refused bronchoscopic examination, and oral prednisolone (0.5 mg/kg/day) improved the symptoms; however, the mass shadow continued to grow. Subsequently, bronchoscopy revealed mucus plugs and an endobronchial tumour with a whitish surface. The tumour was surgically resected, and the pathological diagnosis was a coexistence of ABPM and pulmonary pleomorphic carcinoma. To the best of our knowledge, this is the first case of ABPM developing at the site of pulmonary pleomorphic carcinoma. Careful bronchoscopic examinations and histopathological evaluations of the surgical specimen led to a prompt and accurate diagnosis.
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Gastroesophageal reflux disease (GERD) is one of the most common comorbidities of chronic obstructive pulmonary disease (COPD). Decreased lower and upper esophageal sphincter pressures, esophageal dysmotility, high transdiaphragmatic pressure, and decreased saliva secretion have been implicated as mechanisms leading to the development of GERD in COPD. Clinically, comorbid GERD in COPD is reportedly associated with worse symptoms, quality of life, and lung function, as well as a high risk of exacerbations. Aspiration of regurgitation and the cholinergic-mediated esophagobronchial reflex play a significant role in the pathophysiology. Abnormal swallowing reflexes and discoordination of swallowing can worsen aspiration. The diagnosis of GERD is not based on a single criterion; however, various approaches, including questionnaires and endoscopic evaluations, can be widely applied in clinical settings. Due to the increased risk of esophageal and gastric cancers in patients with COPD, the threshold for endoscopic examination should be low. Acid inhibitory agents, such as proton pump inhibitors and histamine H2 receptor antagonists, and prokinetic agents, including mosapride and itopride, are clinically used to treat GERD. Endoscopic fundoplication can be performed in patients with GERD refractory to medical treatment. There is still insufficient evidence, but an increasing number of studies have suggested the clinical efficacy of treatment in patients with COPD and GERD. As GERD is an evaluative and treatable common disease, and access to evaluation and treatment is relatively easy, clinicians should provide adequate care for GERD in the management of COPD.
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Refluxo Gastroesofágico , Doença Pulmonar Obstrutiva Crônica , Refluxo Gastroesofágico/fisiopatologia , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/diagnóstico , Humanos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/complicações , Qualidade de Vida , Inibidores da Bomba de Prótons/uso terapêutico , Fundoplicatura , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , ComorbidadeRESUMO
Obstructive sleep apnea (OSA) causes excessive daytime sleepiness, impaired daytime functioning, and an increased risk of cardiovascular diseases. Continuous positive airway pressure (CPAP) is a highly effective therapy for moderate to severe OSA. Although CPAP adherence is commonly assessed using a 4-hthreshold, determining the optimal usage time based on clinical outcomes is crucial. While subjective sleepiness often improves with ≥4 h of CPAP usage, an extended duration (≥6 h) may be necessary to impact objective sleepiness. CPAP demonstrated a modest yet clinically meaningful dose-dependent effect on lowering blood pressure. For patients seeking antihypertensive benefits from CPAP therapy, the goal should extend beyond 4 h of use to maximize the therapeutic impact. Recognizing individual variations in sleep duration and responses to CPAP therapy is essential. The adoption of 'individualized goals for CPAP use,' outlining target times for specific outcomes, should also consider an individual's total sleep duration, including periods without CPAP. The impact of CPAP on clinical outcomes may vary, even with the same duration of CPAP use, depending on the period without CPAP use, particularly during the first or second half of sleep. Patients who remove or initiate CPAP midway or have a low CPAP usage frequency may require different forms of guidance. Tailoring patient education to address CPAP usage patterns may be necessary to enhanced satisfaction, self-efficacy, and adherence to therapy. Management of CPAP treatment should be personalized to meet individual needs and adapted based on specific response patterns for achieving treatment efficacy.
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Pressão Positiva Contínua nas Vias Aéreas , Cooperação do Paciente , Apneia Obstrutiva do Sono , Apneia Obstrutiva do Sono/terapia , Humanos , Fatores de Tempo , Educação de Pacientes como Assunto , Sono/fisiologia , Resultado do Tratamento , Pressão Sanguínea , Índice de Gravidade de DoençaRESUMO
Sarcoidosis is a multisystemic granulomatous disease that is frequently localized in the lungs and lymph nodes. We herein report a case of pulmonary sarcoidosis secondary to shin'iseihaito administration. During remission with 5 mg prednisolone/day of maintenance treatment, chest computed tomography revealed a mass in the left lower lobe with re-enlarged bilateral hilar/mediastinal lymph nodes. Transbronchial lung biopsy of the mass and endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes revealed adenocarcinoma and noncaseating granulomas, respectively. Based on these findings, the patient was diagnosed with sarcoidosis recurrence associated with lung cancer without cancer metastasis. We present the case of sarcoidosis recurrence associated with lung cancer after drug-induced pulmonary sarcoidosis with lung injury. To our knowledge, this is the first report of sarcoidosis triggered by drug administration and lung cancer. Histological diagnosis of mediastinal lymphadenopathy with lung cancer is essential for differentiating metastasis from sarcoidosis.
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BACKGROUND: Interstitial lung abnormalities (ILAs) on CT may affect the clinical outcomes in patients with chronic obstructive pulmonary disease (COPD), but their quantification remains unestablished. This study examined whether artificial intelligence (AI)-based segmentation could be applied to identify ILAs using two COPD cohorts. METHODS: ILAs were diagnosed visually based on the Fleischner Society definition. Using an AI-based method, ground-glass opacities, reticulations, and honeycombing were segmented, and their volumes were summed to obtain the percentage ratio of interstitial lung disease-associated volume to total lung volume (ILDvol%). The optimal ILDvol% threshold for ILA detection was determined in cross-sectional data of the discovery and validation cohorts. The 5-year longitudinal changes in ILDvol% were calculated in discovery cohort patients who underwent baseline and follow-up CT scans. RESULTS: ILAs were found in 32 (14%) and 15 (10%) patients with COPD in the discovery (n = 234) and validation (n = 153) cohorts, respectively. ILDvol% was higher in patients with ILAs than in those without ILA in both cohorts. The optimal ILDvol% threshold in the discovery cohort was 1.203%, and good sensitivity and specificity (93.3% and 76.3%) were confirmed in the validation cohort. 124 patients took follow-up CT scan during 5 ± 1 years. 8 out of 124 patients (7%) developed ILAs. In a multivariable model, an increase in ILDvol% was associated with ILA development after adjusting for age, sex, BMI, and smoking exposure. CONCLUSION: AI-based CT quantification of ILDvol% may be a reproducible method for identifying and monitoring ILAs in patients with COPD.
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Inteligência Artificial , Doenças Pulmonares Intersticiais , Doença Pulmonar Obstrutiva Crônica , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Idoso , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Estudos Prospectivos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Estudos Longitudinais , Pulmão/diagnóstico por imagem , Estudos TransversaisRESUMO
Immune checkpoint inhibitors can cause a range of immune-related adverse events, including myositis, Takotsubo cardiomyopathy, and myasthenia gravis. We herein report a rare case of a 78-year-old man with concurrent durvalumab-induced myositis, Takotsubo-like morphological changes caused by myocarditis, and myasthenia gravis. The patient initially required invasive ventilation and exhibited symptoms of myasthenia gravis after treatment with high-dose steroids. However, he subsequently achieved successful recovery after the administration of intravenous immunoglobulin, plasmapheresis, and high-dose steroids. We advocate vigilant neurological monitoring of patients with immune checkpoint inhibitor-induced myositis, including the assessment of ptosis and other relevant signs, so that prompt treatment can be initiated at the time of emergence or progression of immune checkpoint inhibitor-induced myasthenia gravis.
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We propose two types of novel morphological metrics for quantifying the geometry of tubular structures on computed tomography (CT) images. We apply our metrics to identify irregularities in the airway of patients with chronic obstructive pulmonary disease (COPD) and demonstrate that they provide complementary information to the conventional metrics used to assess COPD, such as the tissue density distribution in lung parenchyma and the wall area ratio of the segmented airway. The three-dimensional shape of the airway and its abstraction as a rooted tree with the root at the trachea carina are automatically extracted from a lung CT volume, and the two metrics are computed based on a mathematical tool called persistent homology; treeH0 quantifies the distribution of branch lengths to assess the complexity of the tree-like structure and radialH0 quantifies the irregularities in the luminal radius along the airway. We show our metrics are associated with clinical outcomes.
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Algoritmos , Pulmão , Doença Pulmonar Obstrutiva Crônica , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Imageamento Tridimensional/métodos , Traqueia/diagnóstico por imagemRESUMO
Severe asthma affects approximately 5%-10% of patients with asthma. Herein, we describe a case of non-type 2 asthma that progressively worsened over the years. An 80-year-old woman was diagnosed with asthma 11 years back. She experienced repeated exacerbations requiring treatment with systemic corticosteroid despite therapy with medications including high-dose inhaled corticosteroids/long-acting beta-agonists plus long-acting muscarinic antagonist. The patient presented with non-eosinophilic asthma. Therefore, the patient was initially treated with bronchial thermoplasty, which was effective for 1 year only. Treatment with bronchial thermoplasty, benralizumab, dupilumab, and mepolizumab was ineffective. The fourth treatment, which included tezepelumab, was initiated. The patient's symptoms and quality of life improved significantly. This is the first case of a patient who did not respond to sequential bronchial thermoplasty, benralizumab, dupilumab, and mepolizumab but who presented with good clinical response to tezepelumab. Therefore, tezepelumab may be useful for patients with non-type 2 asthma.
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Chronic eosinophilic pneumonia (CEP) is an eosinophilic lung disease. Treatment for CEP includes corticosteroids; however, CEP often recurs. A 53-year-old woman was referred to our hospital because of poorly controlled asthma. She was treated with combination of moderate-dose inhaled corticosteroid (ICS), a long-acting ß2-agonist (LABA), and betamethasone/dexchlorpheniramine. She was switched to single-inhaler triple therapy, after which her asthma control improved; thus, betamethasone/dexchlorpheniramine was discontinued. Ten weeks later, she was diagnosed with CEP due to marked eosinophilia and pulmonary eosinophilic infiltrates. Oral corticosteroid treatment was initiated, symptoms improved, and peripheral blood eosinophilia decreased with improved infiltrative shadows. Remission induction therapy was initiated with benralizumab combined with corticosteroid therapy. Eosinophilia and inflammatory responses decreased. After 7 months, corticosteroid was discontinued, and she was treated with benralizumab alone. She remained in remission for 4 months. This case suggests that benralizumab may be useful as a remission induction therapy in patients with CEP.
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INTRODUCTION: Air-trapping affects clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) and may be detected by reactance at 5 Hz (X5) on respiratory oscillometry because X5 sensitively reflects the elasticity of the chest wall, airway and lung. However, the longitudinal association between X5 and air-trapping remains to be explored. This study aimed to test whether longitudinal changes in X5 could be associated with air-trapping progression, exacerbations, and mortality in patients with COPD. METHODS: In this prospective COPD observational study, the follow-up period consisted of the first 4 years to obtain longitudinal changes in X5 and residual volume (RV) and number of exacerbations and the remaining years (year 4 to 10) to test mortality. Patients were divided into large, middle, and small X5 decline groups based on the tertiles of longitudinal change in X5, and mortality after 4 years was compared between the groups. RESULTS: Patients with COPD (n = 114) were enrolled. The large X5 decline group (n = 38) showed a greater longitudinal change in RV and more exacerbations compared with the small X5 decline group (n = 39) in multivariable models adjusted for age, sex, body mass index, and smoking history. Long-term mortality after the 4-year follow-up was higher in the large X5 decline group than in the small X5 decline group (hazard ratio [95 % confidence interval] = 8.37[1.01, 69.0]) in the multivariable Cox proportional hazard model. CONCLUSION: Longitudinal changes in respiratory reactance could be associated with progressive air-trapping, exacerbation frequency, and increased mortality in patients with COPD.
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Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos Prospectivos , Volume Expiratório Forçado , Espirometria , PulmãoRESUMO
There have been several reports of drug-induced lung injury caused by molecular-targeted agents. Additionally, medical history of interstitial lung disease and chest irradiation are established risk factors for the development and progression of drug-induced lung injury. Moreover, the presence of fibrosis on chest computed tomography before treatment is a predictive factor for the appearance of pneumonia induced by anticancer drugs. Accordingly, patients with a history of interstitial lung disease or pneumonitis were excluded from clinical trials of dabrafenib and trametinib combination therapy for patients with previously treated BRAF V600E-mutant metastatic non-small-cell lung cancer. This article presents a case of successful dabrafenib and trametinib combination therapy in a patient with BRAF V600E-mutant non-small-cell lung cancer who had a history of radiation pneumonitis and developed recurrence after conventional chemoradiotherapy.
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Recent advances in imaging analysis have enabled evaluation of ventilation and perfusion in specific regions by chest computed tomography (CT) and magnetic resonance imaging (MRI), in addition to modalities including dynamic chest radiography, scintigraphy, positron emission tomography (PET), ultrasound, and electrical impedance tomography (EIT). In this review, an overview of current functional imaging techniques is provided for each modality. Advances in chest CT have allowed for the analysis of local volume changes and small airway disease in addition to emphysema, using the Jacobian determinant and parametric response mapping with inspiratory and expiratory images. Airway analysis can reveal characteristics of airway lesions in chronic obstructive pulmonary disease (COPD) and bronchial asthma, and the contribution of dysanapsis to obstructive diseases. Chest CT is also employed to measure pulmonary blood vessels, interstitial lung abnormalities, and mediastinal and chest wall components including skeletal muscle and bone. Dynamic CT can visualize lung deformation in respective portions. Pulmonary MRI has been developed for the estimation of lung ventilation and perfusion, mainly using hyperpolarized 129Xe. Oxygen-enhanced and proton-based MRI, without a polarizer, has potential clinical applications. Dynamic chest radiography is gaining traction in Japan for ventilation and perfusion analysis. Single photon emission CT can be used to assess ventilation-perfusion (VË/QË) mismatch in pulmonary vascular diseases and COPD. PET/CT VË/QË imaging has also been demonstrated using "Galligas". Both ultrasound and EIT can detect pulmonary edema caused by acute respiratory distress syndrome. Familiarity with these functional imaging techniques will enable clinicians to utilize these systems in clinical practice.
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Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Effective use of lung volume data measured on computed tomography (CT) requires reference values for specific populations. This study examined whether an equation previously generated for multiple ethnic groups in the United States, including Asians predominantly composed of Chinese people, in the Multi-Ethnic Study of Atherosclerosis (MESA) could be used for Japanese people and, if necessary, to optimize this equation. Moreover, the equation was used to characterize patients with chronic obstructive pulmonary disease (COPD) and lung hyperexpansion. METHODS: This study included a lung cancer screening CT cohort of asymptomatic never smokers aged ≥40 years from two institutions (n = 364 and 419) to validate and optimize the MESA equation and a COPD cohort (n = 199) to test its applicability. RESULTS: In all asymptomatic never smokers, the variance explained by the predicted values (R2) based on the original MESA equation was 0.60. The original equation was optimized to minimize the root mean squared error (RMSE) by adjusting the scaling factor but not the age, sex, height, or body mass index terms of the equation. The RMSE changed from 714 ml in the original equation to 637 ml in the optimized equation. In the COPD cohort, lung hyperexpansion, defined based on the 95th percentile of the ratio of measured lung volume to predicted lung volume in never smokers (122 %), was observed in 60 (30 %) patients and was associated with centrilobular emphysema and air trapping on inspiratory/expiratory CT. CONCLUSIONS: The MESA equation was optimized for Japanese middle-aged and elderly adults.
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População do Leste Asiático , Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Idoso , Humanos , Pessoa de Meia-Idade , Detecção Precoce de Câncer , Volume Expiratório Forçado , Japão , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Medidas de Volume Pulmonar , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Valores de ReferênciaRESUMO
Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition with fewer treatments available as the severity increases. Previous systematic reviews have demonstrated the benefits of long-term macrolide use. However, the therapeutic differences between different macrolides and the optimal duration of use remain unclear. Methods: A systematic review and meta-analysis were conducted to assess the effectiveness of long-term macrolide use in reducing COPD exacerbations, compare the therapeutic differences among macrolides, and determine the appropriate treatment duration. Four databases (PubMed, Cochrane Library, Web of Science, and ICHU-SHI) were searched until 20 March 2023, and a random-effects model was used to calculate the pooled effect. Results: The meta-analysis included nine randomized controlled trials involving 1965 patients. The analysis revealed an odds ratio (OR) of 0.34 (95% confidence interval [CI] 0.19, 0.59, p < 0.001) for the reduction in exacerbation frequency. Notably, only azithromycin or erythromycin showed suppression of COPD exacerbations. The ORs for reducing exacerbation frequency per year and preventing hospitalizations were -0.50 (95% CI: -0.81, -0.19; p = 0.001) and 0.60 (95% CI: 0.3, 0.97; p = 0.04), respectively. Statistical analyses showed no significant differences between three- and six-month macrolide prescriptions. However, studies involving a twelve-month prescription showed an OR of 0.27 (95% CI: 0.11, 0.68; p = 0.005; I2 = 81%). Although a significant improvement in St George's Respiratory Questionnaire (SGRQ) total scores was observed with a mean difference of -4.42 (95% CI: -9.0, 0.16; p = 0.06; I2 = 94%), the minimal clinically important difference was not reached. While no adverse effects were observed between the two groups, several studies have reported an increase in bacterial resistance. Conclusions: Long-term use of azithromycin or erythromycin suppresses COPD exacerbations, and previous studies have supported the advantages of a 12-month macrolide prescription over a placebo.
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Introduction: Airway eosinophilic inflammation is a pathological feature in a subgroup of patients with COPD and in some smokers with a high COPD risk. Although blood eosinophil count is used to define eosinophilic COPD, the association between blood eosinophil count and airway eosinophilic inflammation remains controversial. This cross-sectional study tested this association in smokers with and without COPD while considering potential confounders, such as smoking status and comorbidities. Methods: Lung specimens were obtained from smokers with and without COPD and non-COPD never-smokers undergoing lung lobectomy. Those with any asthma history were excluded. The infiltration of eosinophils into the small airway wall was quantified on histological sections stained with major basic protein (MBP). Results: The number of airway MBP-positive cells was greater in smokers (n=60) than in never-smokers (n=14). Smokers with and without COPD (n=30 each) exhibited significant associations between blood eosinophil count and airway MBP-positive cells (ρ=0.45 and 0.71). When smokers were divided into the high and low airway MBP groups based on their median value, blood eosinophil count was higher in the high-MBP group, with no difference in age, smoking status, comorbidities, emphysema or coronary artery calcification on computed tomography, and inhaled corticosteroid (ICS) use. The association between greater blood eosinophil count and the high-MBP group was confirmed in multivariable models adjusted for smoking status, airflow limitation and ICS use. Conclusion: The blood eosinophil count may reflect eosinophilic inflammation in the small airways in smokers with and without COPD.
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Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction on spirometry and symptoms such as dyspnea on exertion and chronic cough with sputum production, thus making it a significant healthcare issue worldwide. Japanese patients with COPD have unique characteristics compared to patients in Western countries, including older age and lower exacerbation frequency. The Japanese Respiratory Society (JRS) published the 6th edition of the COPD guideline in June 2022. This article introduces the management goals of COPD and describes its management during the stable phase, as outlined in the guideline. Management goals include improving the current status, such as the symptoms, quality of life (QOL), exercise tolerance, and physical activity, and reducing future risks through prevention of exacerbation and suppression of disease progression to prevent shortening of healthy life expectancy. Management plans should include avoidance of causative substances, assessment of disease severity, and personalized treatment plans. Pharmacotherapy using inhalation bronchodilators is a key component of the treatment of stable COPD. Bronchodilators, including short- and long-acting dilators, are commonly used to relieve symptoms and improve QOL. Inhaled corticosteroids (ICSs) are used in combination with long-acting bronchodilators, especially in patients with asthma and COPD overlap, or those experiencing frequent exacerbation of eosinophilia. Combination therapy with a long-acting muscarinic antagonist (LAMA), a long-acting beta 2 agonist (LABA), and ICS is expected to improve QOL and respiratory function and reduce mortality and exacerbation compared to the LAMA + LABA combination. Non-pharmacological therapies, including smoking cessation and pulmonary rehabilitation, should also be considered.
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Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Humanos , Administração por Inalação , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2 , Broncodilatadores/uso terapêutico , Quimioterapia Combinada , População do Leste Asiático , Objetivos , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapiaRESUMO
Rationale: Subjects with preserved ratio impaired spirometry (PRISm) experience increased respiratory symptoms, although they present heterogeneous characteristics. However, the longitudinal changes in these symptoms and respiratory function are not well known. Objectives: To investigate PRISm from the viewpoint of respiratory symptoms in a longitudinal, large-scale general population study. Methods: The Nagahama study included 9,789 inhabitants, and a follow-up evaluation was conducted after 5 years. Spirometry and self-administered questionnaires regarding respiratory symptoms, including prolonged cough, sputum and dyspnea, and comorbidities were conducted. Results: In total, 9,760 subjects were analyzed, and 438 subjects had PRISm. Among the subjects with PRISm, 53% presented with respiratory symptoms; dyspnea was independently associated with PRISm. Follow-up assessment revealed that 73% of the subjects with PRISm with respiratory symptoms were consistently symptomatic, whereas 39% of the asymptomatic subjects with PRISm developed respiratory symptoms within 5 years. In addition, among subjects with respiratory symptoms without airflow limitation at baseline, PRISm was a risk factor for the development of airflow limitation independent of smoking history and comorbidities. Conclusions: This study demonstrated that 53% of the subjects with PRISm had respiratory symptoms; dyspnea was a distinct characteristic of PRISm. Approximately three-fourths of the symptomatic subjects with PRISm consistently complained of respiratory symptoms within 5 years. Together with our result that PRISm itself is an independent risk factor for the development of chronic obstructive pulmonary disease among subjects with respiratory symptoms, the clinical course of subjects with PRISm with symptoms requires careful monitoring.