Kunihiko Terada

Impact of gastro-oesophageal reflux disease symptoms on COPD exacerbation

Background: The association between gastro-oesophageal reflux disease (GORD) and chronic obstructive pulmonary disease (COPD) exacerbation has so far remained unclear. Objective: To prospectively establish the clinical significance of GORD symptoms on exacerbation. Methods: 82 patients with COPD and 40 age matched controls were enrolled in this study. Symptoms were evaluated by a questionnaire using the Frequency Scale for the Symptoms of GORD (FSSG). Patients with COPD were prospectively surveyed for 6 months, and episodes of exacerbation were identified using a diary based on modified Anthonisen’s criteria. Exhaled breath condensate (EBC) pH was measured in both groups, and induced sputum was evaluated in patients with COPD. Results: Positive GORD symptoms were reported in 22 (26.8%) patients with COPD and in five (12.5%) controls (p = 0.10). The frequency of exacerbations was significantly associated with the FSSG score (p = 0.03, r = 0.24, 95% CI 0.02 to 0.43). Multiple regression analysis revealed that GORD symptoms were significantly associated with the occurrence of exacerbations (p<0.01; relative risk 6.55, 95% CI 1.86 to 23.11). EBC pH was inversely correlated with FSSG score in both groups (p = 0.01, r = –0.37, 95% CI –0.55 to −0.14 in patients with COPD, and p<0.01, r = –0.45, 95% CI –0.67 to −0.16 in control subjects). Conclusions: GORD symptoms were identified as an important factor associated with COPD exacerbation.

Relationship Between Pulmonary Emphysema and Osteoporosis Assessed by CT in Patients With COPD

BACKGROUND Osteoporosis is one of the important systemic features of COPD. Although COPD itself is regarded as one risk factor for osteoporosis, the relationship between the extent of emphysema and reduced bone density is still unclear. Our first aim was therefore to measure vertebral bone density and the percentage of low-attenuation area (LAA%) in the lungs using chest CT scans in COPD patients. Our second aim was to investigate the relationships among CT scan measurements, anthropometric parameters, and pulmonary function. METHODS Chest CT scans and pulmonary function tests were performed in 65 male patients with COPD. Using CT images, the CT scan density of the thoracic and lumbar vertebrae (T4, T7, T10, and L1) and the LAA% were measured quantitatively, and their correlations were analyzed. RESULTS Linear regression analyses revealed that LAA% had a significant negative correlation with bone mineral density (BMD) [r = -0.522]. In addition, multiple regression analysis showed that only LAA% and body mass index (BMI) were predictive of BMD among age, BMI, smoking index, FEV(1), arterial blood gas, and LAA%. CONCLUSIONS The extent of pulmonary emphysema significantly correlated with reduced bone density. Our study suggested that COPD itself could be a risk factor for osteoporosis and that chest CT scanning is useful for the management of COPD as a systemic disease.

Impact of Exacerbations on Emphysema Progression in Chronic Obstructive Pulmonary Disease

RATIONALE Low-attenuation areas assessed by computed tomography reflect the extent of pathological emphysema and correlate with airflow limitation and mortality in patients with chronic obstructive pulmonary disease. The cumulative size distribution of low-attenuation area clusters follows a power law characterized by an exponent, D. The values of D reflect the complexity of the terminal airspace geometry and sensitively detect alveolar structural changes. Exacerbations of chronic obstructive pulmonary disease have a negative impact on lung function and prognosis. However, the impact on emphysema progression remains unclear. OBJECTIVES We investigated the relationship between exacerbation and emphysema progression assessed by computed tomography in patients with chronic obstructive pulmonary disease. METHODS Exacerbations were prospectively recorded for 2 years. Annual changes in computed tomography parameters of emphysema were compared between patients with and without a history of exacerbations. MEASUREMENTS AND MAIN RESULTS In patients with exacerbations, increases in the percentage of low-attenuation areas and decreases in D were greater than in patients without exacerbations. To interpret these results, we established a novel simulation model and found that not only enlargement of preexisting low-attenuation areas but also coalescence of adjoining low-attenuation areas due to alveolar wall destruction caused emphysema progression in patients with exacerbations. CONCLUSIONS This is the first longitudinal study to demonstrate that exacerbations are involved in emphysema progression in patients with chronic obstructive pulmonary disease. Emphysema progression should be evaluated as part of the outcomes of exacerbations in the management of chronic obstructive pulmonary disease.

Abnormal Swallowing Reflex and COPD Exacerbations

BACKGROUND It is unclear whether an abnormal swallowing reflex affects COPD exacerbations. This study investigated the prevalence of abnormal swallowing reflexes and its relationship with COPD exacerbation prospectively. We also clarified its association with gastroesophageal reflux disease (GERD) and airway bacterial colonization. METHODS Swallowing reflex and serum C-reactive protein (CRP) levels were examined in subjects with stable COPD and in control subjects. Concurrently, GERD symptoms were assessed using a self-reported questionnaire, and sputum bacterial cultures were investigated in the same subjects. Exacerbations were counted prospectively during the following 12 months. RESULTS The study group comprised 67 subjects with COPD and 19 controls. The prevalence of abnormal swallowing reflex was significantly higher in subjects with COPD (22/67) than controls (1/19; P = .02). Among subjects with COPD, the serum CRP level, GERD symptoms, isolation of sputum bacteria, and the frequency of exacerbations were significantly increased in those with abnormal swallowing reflexes compared with controls (2.72 vs 1.04 mg/L, P = .04, for serum CRP level; 6.75 vs 4.10 points, P = .04, for GERD symptoms; 5/11 vs 3/22, P = .04, for the isolation of sputum bacteria; and 2.82 vs 1.56/y, P = .007, for the annual frequency of exacerbations). Multivariable analysis confirmed that abnormal swallowing reflex was significantly associated with frequent exacerbations (>or= 3/y; P = 0.01). CONCLUSIONS Abnormal swallowing reflexes frequently occurred in subjects with COPD and predisposed them to exacerbations. Abnormal swallowing reflexes in COPD might be affected by the comorbidity of GERD, and cause bacterial colonization.

Relationship between peripheral airway function and patient-reported outcomes in COPD: a cross-sectional study

BackgroundHealth status, dyspnea and psychological status are important clinical outcomes in chronic obstructive pulmonary disease (COPD). However, forced expiratory volume in one second (FEV1) measured by spirometry, the standard measurement of airflow limitation, has only a weak relationship with these outcomes in COPD. Recently, in addition to spirometry, impulse oscillometry (IOS) measuring lung resistance (R) and reactance (X) is increasingly being used to assess pulmonary functional impairment.MethodsWe aimed to identify relationships between IOS measurements and patient-reported outcomes in 65 outpatients with stable COPD. We performed pulmonary function testing, IOS, high-resolution computed tomography (CT), and assessment of health status using the St. Georges Respiratory Questionnaire (SGRQ), dyspnea using the Medical Research Council (MRC) scale and psychological status using the Hospital Anxiety and Depression Scale (HADS). We then investigated the relationships between these parameters. For the IOS measurements, we used lung resistance at 5 and 20 Hz (R5 and R20, respectively) and reactance at 5 Hz (X5). Because R5 and R20 are regarded as reflecting total and proximal airway resistance, respectively, the fall in resistance from R5 to R20 (R5-R20) was used as a surrogate for the resistance of peripheral airways. X5 was also considered to represent peripheral airway abnormalities.ResultsR5-R20 and X5 were significantly correlated with the SGRQ and the MRC. These correlation coefficients were greater than when using other objective measurements of pulmonary function, R20 on the IOS and CT instead of R5-R20 and X5. Multiple regression analyses showed that R5-R20 or X5 most significantly accounted for the SGRQ and MRC scores.ConclusionsIOS measurements, especially indices of peripheral airway function, are significantly correlated with health status and dyspnea in patients with COPD. Therefore, in addition to its simplicity and non-invasiveness, IOS may be a useful clinical tool not only for detecting pulmonary functional impairment, but also to some extent at least estimating the patients quality of daily life and well-being.

Longitudinal study of airway dimensions in chronic obstructive pulmonary disease using computed tomography.

Background and objective:  Chest CT has been widely used for the evaluation of structural changes in lung parenchyma and airways in cross‐sectional studies. There has been no report on the annual changes in airway dimensions as assessed by CT in COPD patients. The objective of this study was to investigate the annual changes in airway dimensions and lung attenuation using CT in patients with COPD and to evaluate the correlations among annual changes in CT measurements and pulmonary function.

Sputum YKL-40 Levels and Pathophysiology of Asthma and Chronic Obstructive Pulmonary Disease

Background: Recent evidence suggests that YKL-40, also called chitinase-3-like-1 protein, is involved in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). Details of sputum YKL-40 in asthma and COPD, however, remain unknown. Objectives: To clarify associations of sputum YKL-40 levels with clinical indices in asthma and COPD. Methods: Thirty-nine patients with asthma, 14 age-matched never-smokers as controls, 45 patients with COPD, and 7 age-matched smokers as controls were recuited for this study. Sputum YKL-40 levels were measured and YKL-40 expression in sputum cells was evaluated by immunocytochemistry. Results: Sputum YKL-40 levels were higher in patients with COPD (346 ± 325 ng/ml) than in their smoker controls (125 ± 122 ng/ml; p < 0.05), but were not significantly different between patients with asthma (117 ± 170 ng/ml) and their controls (94 ± 44 ng/ml; p = 0.15). In patients with asthma only, sputum YKL-40 levels were positively correlated with disease severity (r = 0.34, p = 0.034) and negatively correlated with pre- and postbronchodilator %FEV1 (r = –0.47 and –0.42, respectively; p < 0.01) and forced mid-expiratory flow (r = –0.48 and –0.46, respectively, p < 0.01). Sputum YKL-40 levels were positively correlated with sputum neutrophil counts in asthma (r = 0.55, p < 0.001) and with neutrophil and macrophage counts in COPD (r = 0.45 and 0.65, respectively, p < 0.01). YKL-40 was expressed in the cytoplasm of sputum neutrophils and macrophages in all groups. Conclusions: Elevated sputum YKL-40 reflects airflow obstruction in asthma whereas the roles of YKL-40 in the proximal airways in COPD remain to be elucidated.

Cough-reflex sensitivity to inhaled capsaicin in COPD associated with increased exacerbation frequency

Background and objective:  The causes of exacerbations in COPD patients are poorly understood. This study examined the association between cough‐reflex sensitivity in patients with stable COPD and the frequency of subsequent exacerbations.

Relationship between periodontitis-related antibody and frequent exacerbations in chronic obstructive pulmonary disease.

Background To identify patients with chronic obstructive pulmonary disease (COPD) who are susceptible to frequent exacerbations is important. Although periodontitis aggravated by poor oral hygiene might increase the risk of lower respiratory tract infection, the relationship between periodontitis and COPD exacerbations remains unknown. This prospective cohort study investigates the relationship between periodontitis-related antibody and exacerbation frequency over a one-year period. Methods We assessed an IgG antibody titer against Porphyromonas gingivalis, which is a major pathogen of periodontitis, and then prospectively followed up 93 individuals over one year to detect exacerbations. Results The numbers of exacerbations and the rate of individuals with frequent exacerbations (at least two per year) were significantly lower in patients with higher IgG titer than those with normal IgG titer (0.8 vs. 1.2 per year, p  = 0.045 and 14.3 vs. 38.6%, p  = 0.009, respectively). Multivariate logistic regression analysis showed that being normal-IgG titer for periodontitis-related antibody significantly increased the risk of frequent exacerbations (relative risk, 5.27, 95% confidence interval, 1.30–25.7; p  = 0.019) after adjusting for other possible confounders, such as a history of exacerbations in the past year, disease severity, COPD medication and smoking status. Conclusions Normal-IgG titer for periodontitis-related antibody can be an independent predictor of frequent exacerbations. Measuring periodontitis-related antibody titers might be useful to identify patients with susceptibility to frequent exacerbations so that an aggressive prevention strategy can be designed.

The impact of tiotropium for exercise induced bronchoconstriction

Background: Exercise induced bronchoconstriction (EIB) occurs frequently among athletes. Standard prevention plus pharmacological treatment cannot relieve EIB induced symptom in a part of patients. The usefulness of tiotropium on uncontrolled EIB has so far remained unclear. In this study, we report 8 cases of the difficult-to-control EIB treated with tiotropium. Objective: To examine the impact of tiotropium on the difficult-to-control EIB. Methods: In total, 8 cases of EIB were enrolled in this study. All the patients cannot achieve symptom-control with standard prevention and pharmacological treatment with rescue use of inhaled short-acting beta 2-agonist (SABA) and maintenance with inhaled corticosteroid plus long-acting beta 2-agonist. The delivered dose of tiotropium 5 microgram via respimat inhaler was added on maintenance medication. Symptom and the frequency of additional SABA use were compared before and 2 to 4 weeks after the initiation of tiotropium. Symptom was evaluated with visual analog scale (VAS) scale. More than 50% reduction of VAS scale plus rescue SABA use were defined “effective”. Results: Demographics of 8 cases were follows: mean age was 43 (15 - 56), 4 males, smoking status: one current, 2 former, and 5 never smokers, %FEV1 was 92.0 (78.2 - 106.4)％, Fe-NO 22 (14 - 30) ppb. Tiotropium was effective on 6 among 8 cases of difficult-to-control EIB. Conclusions: Tiotropium could be a useful choice to manage difficult-to-control EIB.