Polysomnographic features of low arousal threshold in overlap syndrome involving obstructive sleep apnea and chronic obstructive pulmonary disease.

PURPOSE: In patients with overlap syndrome (OVS), the pathophysiologies of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease can interact with one another. Focusing on low arousal threshold, the authors evaluated polysomnographic features of OVS patients. METHODS: This retrospective, multicenter study was conducted at three hospitals in Japan. Patients aged ≥ 60 years who underwent polysomnography and pulmonary function testing were reviewed. Severity of airflow limitation (AFL) was classified according to the Global Initiative for Chronic Obstructive Lung Disease criteria. Low arousal threshold was predicted based on the following polysomnography features: lower apnea-hypopnea index (AHI); higher nadir oxygen saturation, and larger hypopnea fraction of total respiratory events. These features were compared among patients with only OSA (n = 126), OVS with mild AFL (n = 16), and OVS with moderate/severe AFL (n = 22). RESULTS: A low arousal threshold was more frequently exhibited by OVS patients with moderate/severe AFL than by those with OSA only (p = 0.016) and OVS with mild AFL (p = 0.026). As forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) decreased in OVS patients, the mean length of apnea decreased (r = 0.388, p = 0.016), hypopnea fractions increased (r = - 0.337, p = 0.039), and AHI decreased (r = 0.424, p = 0.008). FEV1/FVC contributed to low arousal threshold independent of age, sex, smoking history, hospital, or body mass index in all subjects (OR 0.946 [95% CI 0.909-0.984]) and in OVS patients (OR 0.799 [95% CI 0.679-0.940]). CONCLUSIONS: This study first described peculiar polysomnographic features in OVS patients with moderate/severe AFL, suggesting a high prevalence of low arousal threshold.

Effectiveness of home-based exercise in older patients with advanced chronic obstructive pulmonary disease: A 3-year cohort study.

AIM: To determine whether home-based exercise can improve clinical outcomes in older patients with advanced chronic obstructive pulmonary disease using long-term oxygen therapy. METHODS: Information was provided to improve chronic obstructive pulmonary disease self-management before the onset of the present prospective 3-year cohort study. Patients selected either home-based exercise using a lower-limb cycle machine (ergo-bicycle; group E), or usual exercise (group U). To assess self-management, the Lung Information Needs Questionnaire was evaluated every 6 months. Clinical outcomes included the 6-min walk test, pulmonary function tests, the body mass index, airflow obstruction, dyspnea and exercise index, St. George's respiratory questionnaire, and the number of exacerbations and hospitalizations. RESULTS: A total of 136 patients (group E = 72; group U = 64), with a mean age of 74.2 years were enrolled. Total Lung Information Needs Questionnaire scores improved over 3 years for group E (P = 0.003). The distance of the 6-min walk test was well maintained in group E, but significantly decreased in group U (P < 0.001). The percentage of forced expiratory volume in 1 s at baseline was lower in group E (P = 0.016), but was maintained over 3 years, whereas a significant reduction was seen in group U (P = 0.001). The body mass index, airflow obstruction, dyspnea and exercise index significantly worsened in both groups over 3 years (group E: P = 0.011; group U: P < 0.001), whereas a significant decrease in the number of exacerbations was noted in group E (P = 0.009). CONCLUSIONS: Patients who undertook home-based exercise using an ergo-bicycle were able to maintain clinical outcomes including 6-min walk test distance and percentage of forced expiratory volume in 1 s predicted, and recorded fewer exacerbations over 3 years. Geriatr Gerontol Int 2018; 18: 42-49.

Chronic Thromboembolic Pulmonary Hypertension Associated with Chronic Inflammation.

Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the leading causes of severe pulmonary hypertension. According to previously reported studies in the pertinent literature, chronic inflammatory conditions may be implicated in the development of CTEPH. We herein describe the case of a 56-year-old woman who was diagnosed with CTEPH in association with chronic infection. The patient had experienced five episodes of pneumonia in the five years prior to the diagnosis of CTEPH. Blood tests from the previous five years of outpatient follow-up demonstrated that the C-reactive protein level was slightly elevated. This case suggests that a relationship exists between chronic inflammation and CTEPH, and furthermore, may contribute towards elucidating the pathophysiology of CTEPH.

The Neutrophil to Lymphocyte Ratio Is Related to Disease Severity and Exacerbation in Patients with Chronic Obstructive Pulmonary Disease.

Objective Although chronic obstructive pulmonary disease (COPD) is characterized by systemic inflammation, the association between the neutrophil to lymphocyte ratio (NLR; an indicator of inflammation) and the clinical status of COPD has not been well studied. We hypothesized that the NLR is associated with disease severity and exacerbation in COPD patients. Methods We performed blood testing, pulmonary function testing, chest computed tomography, a body composition analysis, and a 6-minute walk test and applied the modified Medical Research Council (MMRC) dyspnea scale for 141 stable COPD patients. In addition, we calculated the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index to evaluate the disease severity. Finally, we examined the association between the NLR and clinical parameters in stable COPD patients, and we further investigated changes in the NLR between exacerbation and the stable state. Results The NLR was positively correlated with the BODE index, extent of emphysema, and MMRC score (p<0.001 for all), while inversely correlated with airflow obstruction (p<0.001), body mass index (p<0.001), fat-free mass index (p=0.001), and the 6-minute walk distance (p<0.001). We obtained the NLR during exacerbation from 49 patients. The NLR was significantly higher at exacerbation compared to the stable state (p<0.001). Conclusion The NLR was associated with disease severity and exacerbation in COPD patients. Therefore, the usefulness of the NLR in COPD patients should be elucidated in clinical settings in future investigations.

Atrial and Ventricular Arrhythmia-Associated Factors in Stable Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Supraventricular and ventricular premature complexes (SVPC and VPC, respectively) are associated with chronic obstructive pulmonary disease (COPD) and with increased mortality in COPD patients. However, there are few reports on the causes of arrhythmia in COPD patients. OBJECTIVES: This study explores the associations between cardiopulmonary dysfunction and COPD by comparing patients with defined arrhythmias (>100 beats per 24 h) and those without, based on 24-hour electrocardiogram (ECG) recordings. METHODS: Patients with arrhythmia underwent a 24-hour ECG and subsequent pulmonary function tests, computed tomography, ECG, 6-min walk test (6MWT), and BODE (body mass index, airflow obstruction, modified Medical Research Council Dyspnoea Scale, exercise capacity) index calculation. RESULTS: Of 103 study patients (71 COPD patients and 32 at-risk patients), 36 had VPC, 45 had SVPC, 20 had both, and 42 had neither. The predicted post-bronchodilator forced expiratory volume in 1 s, the proportion of low-attenuation area on computed tomography, and BODE index values were significantly worse in the SVPC and VPC groups compared with the corresponding reference groups. Patients in the VPC group showed significantly increased right ventricular pressure and increased desaturation in the 6MWT compared with the reference group. In the multivariate analyses, bronchodilator use was a significant risk factor in the SVPC group, whereas in the VPC group, all parameters of the BODE index except for the dyspnoea score were identified as risk factors. CONCLUSIONS: Increased SVPC might be caused by bronchodilator use, whereas increased VPC is likely related to the peculiar pathophysiology of COPD.

Marked improvement in leptomeningeal carcinomatosis and spinal cord metastases following alectinib treatment of crizotinib-resistant, ALK-positive lung adenocarcinoma.

We report a case of 50-year-old Japanese female with anaplastic lymphoma kinase (ALK)-positive, crizotinib-resistant lung adenocarcinoma, whose leptomeningeal carcinomatosis and spinal cord metastases were dramatically improved by the second-generation ALK inhibitor alectinib. Magnetic resonance imaging (MRI) revealed multiple brain metastases at diagnosis of lung cancer. Carboplatin/paclitaxel/bevacizumab chemotherapy was administered, but enlargement of brain tumors was observed after 3 months. Gamma knife radiosurgery was performed and then the patient received second-line chemotherapy with crizotinib. After 4 months brain MRI revealed the development of leptomeningeal carcinomatosis. Despite the patient undergoing whole brain radiotherapy, spinal cord metastases appeared. Third-line chemotherapy with alectinib was initiated for the management of metastases in central nervous system (CNS) including those in the leptomeninges and spine cord. After 3 months, marked tumor responses were observed in both the leptomeningeal carcinomatosis and spinal cord metastases. This report suggests that alectinib is a promising drug for ALK-positive lung adenocarcinoma with CNS metastases.

Long-term effects of gastrectomy in patients with spirometry-defined COPD and patients at risk of COPD: a case-control study.

OBJECTIVE: Comorbidities are characteristic of COPD. However, little is known about the secondary manifestations of COPD in the gastrointestinal tract. Therefore, we aimed to explore the long-term effects of gastrectomy in patients with spirometry-defined COPD or those at risk of COPD. PARTICIPANTS: Subjects included 87 patients either with COPD or at risk of COPD (symptomatic) who underwent gastrectomy between December 2003 and October 2013 (group A), and 174 patients either with COPD or at risk of COPD, matched by age (±5 years), sex, and forced expiratory volume in 1 second (FEV1) as percentage of predicted (FEV1% predicted) (±5%) (group B). METHODS: All patients underwent routine blood chemistry and pulmonary function tests, arterial blood gas analysis, 6-minute walk test (6MWT), high-resolution chest computed tomography scans, and nutritional assessments. RESULTS: The mean duration postgastrectomy was 18.3±15.4 years. The mean FEV1 and FEV1% predicted were 2.07±0.76 L and 74.6±24.5%, respectively. Univariate analysis indicated that group A patients had significantly lower body mass index, fat-free mass index, and serum hemoglobin and albumin concentration (all P=0.00), and walked a significantly shorter distance in the 6MWT (P<0.05). Multivariate linear regression analysis for the distance in the 6MWT indicated that increased residual volume (RV) to total lung capacity (TLC) as percentage of predicted (%RV/TLC) alone was an independent and significant predictor of reduced distances in the 6MWT. CONCLUSION: We concluded that nutritional insufficiency in patients with COPD (or those at risk of COPD) who previously underwent gastrectomy might lead to hyperinflation and consequently, decreased exercise capacity.

Relationship between serum cardiac troponin T level and cardiopulmonary function in stable chronic obstructive pulmonary disease.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) in serum is a useful marker of acute myocardial injury, yet information is limited in patients with chronic obstructive pulmonary disease. We aimed to explore the association between hs-cTnT levels and cardiac and pulmonary dysfunction in patients with stable chronic obstructive pulmonary disease and at-risk individuals. METHODS: We examined community-dwelling adults with/without chronic obstructive pulmonary disease, with a life-long smoking history, current symptoms of dyspnea during exertion, prolonged coughing, and/or sputum. Serum hs-cTnT concentrations were measured, and subjects underwent pulmonary function tests, high-resolution computed tomography of the chest, an echocardiogram, and a 6-minute walking test. RESULTS: Eighty-six stable patients were identified (mean age 65.5 years; predicted forced expiratory volume in 1 second [FEV1% predicted] 75.0%). Their overall mean hs-cTnT level was 0.008 ng/mL. Logarithmically transformed hs-cTnT levels significantly and positively correlated with age, smoking index, serum high-sensitivity C-reactive protein levels, right ventricle systolic pressure, low attenuation area percentage, and brain natriuretic peptide levels (range r=0.231-0.534, P=0.000 to P=0.042). Further, logarithmically transformed hs-cTnT values significantly and negatively correlated with forced vital capacity, FEV1% predicted, diffusion capacity, arterial oxygen tension, and 6-minute walking distance (range r= -0.482 to -0.377, P=0.000 to P=0.002). Multivariate analyses showed that hs-cTnT values varied independently according to the following three parameters: high-sensitivity C-reactive protein levels (B=0.157, ß=0.450, t=3.571, P=0.001), age (B=0.008, ß=0.352, t=2.789, P=0.009), and right ventricular systolic pressure (B=0.008, ß=0.280, t=2.202, P=0.035). CONCLUSION: Even in patients with stable chronic obstructive pulmonary disease, the serum troponin T concentration was controlled by at least three major factors, ie, systemic inflammation, advancing age, and right cardiac overload.

An autopsy study of combined pulmonary fibrosis and emphysema: correlations among clinical, radiological, and pathological features.

BACKGROUND: Clinical evaluation to differentiate the characteristic features of pulmonary fibrosis and emphysema is often difficult in patients with combined pulmonary fibrosis and emphysema (CPFE), but diagnosis of pulmonary fibrosis is important for evaluating treatment options and the risk of acute exacerbation of interstitial pneumonia of such patients. As far as we know, it is the first report describing a correlation among clinical, radiological, and whole-lung pathological features in an autopsy cases of CPFE patients. METHODS: Experts retrospectively reviewed the clinical charts and examined chest computed tomography (CT) images and pathological findings of an autopsy series of 22 CPFE patients, and compared these with findings from 8 idiopathic pulmonary fibrosis (IPF) patients and 17 emphysema-alone patients. RESULTS: All patients had a history of heavy smoking. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC%) was significantly lower in the emphysema-alone group than the CPFE and IPF-alone groups. The percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) was significantly lower in the CPFE group than the IPF- and emphysema-alone groups. Usual interstitial pneumonia (UIP) pattern was observed radiologically in 15 (68.2%) CPFE and 8 (100%) IPF-alone patients and was pathologically observed in all patients from both groups. Pathologically thick-cystic lesions involving one or more acini with dense wall fibrosis and occasional fibroblastic foci surrounded by honeycombing and normal alveoli were confirmed by post-mortem observation as thick-walled cystic lesions (TWCLs). Emphysematous destruction and enlargement of membranous and respiratory bronchioles with fibrosis were observed in the TWCLs. The cystic lesions were always larger than the cysts of honeycombing. The prevalence of both radiological and pathological TWCLs was 72.7% among CPFE patients, but no such lesions were observed in patients with IPF or emphysema alone (p=0.001). The extent of emphysema in CPFE patients with TWCLs was greater than that in patients without such lesions. Honeycombing with emphysema was also observed in 11 CPFE patients. CONCLUSIONS: TWCLs were only observed in the CPFE patients. They were classified as lesions with coexistent fibrosing interstitial pneumonia and emphysema, and should be considered an important pathological and radiological feature of CPFE.

A comparison of three multidimensional indices of COPD severity as predictors of future exacerbations.

BACKGROUND: Prediction of future exacerbations of chronic obstructive pulmonary disease (COPD) is a major concern for long-term management of this disease. AIM: To determine which of three multidimensional assessment systems (the body mass index, obstruction, dyspnea, and exercise capacity [BODE] index; dyspnea, obstruction, smoking, exacerbations [DOSE] index; or age, dyspnea, obstruction [ADO] index) is superior for predicting exacerbations. METHODS: This was a 2-year prospective cohort study of COPD patients. Pulmonary function tests, the 6-minute walk distance (6MWD), Modified Medical Respiratory Council (MMRC) dyspnea scores, chest computed-tomography measurements, and body composition were analyzed, and predictions of exacerbation by the three assessment systems were compared. RESULTS: Among 183 patients who completed the study, the mean annual exacerbation rate was 0.57 events per patient year, which correlated significantly with lower predicted forced expiratory volume in 1 second (FEV1) (P < 0.001), lower transfer coefficient of the lung for carbon monoxide (%DLco/VA) (P = 0.021), lesser 6MWD (P = 0.016), higher MMRC dyspnea score (P = 0.001), higher DOSE index (P < 0.001), higher BODE index (P = 0.001), higher ADO index (P = 0.001), and greater extent of emphysema (P = 0.002). For prediction of exacerbation, the areas under the curves were larger for the DOSE index than for the BODE and ADO indices (P < 0.001). Adjusted multiple logistic regression identified the DOSE index as a significant predictor of risk of COPD exacerbation. CONCLUSION: In this study, the DOSE index was a better predictor of exacerbations of COPD when compared with the BODE and ADO indices.

Decreased serum transforming growth factor-ß1 concentration with aging is associated with the severity of emphysema in chronic obstructive pulmonary disease.

AIM: Age-associated changes of the lung might increase pathogenetic susceptibility to chronic obstructive pulmonary disease (COPD). Decrement in serum transforming growth factor (TGF)-ß1 concentration is reported in elderly people. As impaired TGF-ß1 signaling could cause emphysema-like changes, we hypothesized that decreased TGF-ß1 with aging is correlated with emphysema. METHODS: Symptomatic patients with or without COPD and healthy normal subjects without COPD were recruited (COPD, n = 182; smoking controls, n = 73; normal, n = 26). We investigated the correlation between TGF-ß1 and extent of emphysema and airway wall thickness, which were defined as the percentage of low-attenuation area (LAA%) and large airway wall area (WA%) on pulmonary high-resolution computed tomography, respectively. The correlation of pulmonary function test parameters and TGF-ß1 was evaluated. TGF-ß1 was determined by enzyme-linked immunosorbent assay. RESULTS: TGF-ß1 significantly decreased with age (P = 0.0009). When the correlation between age and TGF-ß1 was analyzed in each group, a significant inverse correlation was found in COPD patients and smoking controls (P = 0.0095 and 0.0132, respectively), whereas no correlation was observed in healthy older adults. Among COPD patients with severe emphysema, LAA% was inversely correlated with TGF-ß1 (n = 89, P = 0.0104), whereas WA% and pulmonary function test parameters were not. CONCLUSIONS: Although no correlation was found between TGF-ß1 and the severity of COPD, TGF-ß1 significantly decreased as emphysema became more severe. Age-related decrease of TGF-ß1 in COPD might be associated with emphysematous alterations of the lungs in elderly subjects.