Alleviation of Dyspnea and Changes in Physical Activity Level by Air Flow to the Face With a Fan.

BACKGROUND: Dyspnea is an unpleasant subjective symptom and is associated with decreased physical activity level (PAL). Effect of blowing air toward the face has received a great deal of attention as a symptomatic therapy for dyspnea. However, little is known about the duration of its effect and its impact on PAL. Therefore, this study aimed to measure dyspnea severity and changes in dyspnea and PALs with air blasts to the face. METHODS: The trial conducted was open-label, randomized, and controlled. This study included out-patients with dyspnea caused by chronic respiratory deficiency. Subjects were provided a small fan and instructed to blow air toward their faces either twice a day or when having trouble breathing. Subsequently, severity of dyspnea and PALs was measured using visual analog scale and physical activity scale for the elderly (PASE), respectively, before and after 3-week treatment. Amounts of changes in dyspnea and PALs before and after treatment were compared using analysis of covariance. RESULTS: Overall, 36 subjects were randomized, and 34 were analyzed. Mean age was 75.4 y (26 males [76.5%] and 8 females [23.5%]). Visual analog scale score for dyspnea (SD) before treatment was 33 (13.9) mm and 42 (17.5) mm in the control and intervention groups, respectively. PASE score before treatment was 78.0 (45.1) and 57.7 (38.0) in the control and intervention groups, respectively. No significant difference in changes in dyspnea severity and PAL was observed between the 2 groups. CONCLUSIONS: No significant difference was observed for dyspnea and PALs in subjects after blowing air toward their own faces with a small fan for 3 weeks at home. Disease variability and impact of protocol violations were high due to small number of cases. Further studies with a design focused on subject protocol adherence and measurement methods are required to understand impact of air flow on dyspnea and PAL.

Long-term effect of pulmonary rehabilitation in idiopathic pulmonary fibrosis: a randomised controlled trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by worsening dyspnoea and exercise intolerance. RESEARCH QUESTION: Does a long-term pulmonary rehabilitation improve exercise tolerance in patients with IPF treated with standard antifibrotic drugs, which are expected to reduce disease progression? METHODS: This open-label randomised controlled trial was performed at 19 institutions. Stable patients receiving nintedanib were randomised into pulmonary rehabilitation and control groups (1:1). The pulmonary rehabilitation group underwent initial rehabilitation which included twice-weekly sessions of monitored exercise training for 12 weeks, followed by an at-home rehabilitation programme for 40 weeks. The control group received usual care only, without pulmonary rehabilitation. Both groups continued to receive nintedanib. The primary and main secondary outcomes were change in 6 min walking distance (6MWD) and change in endurance time (using cycle ergometry) at week 52. RESULTS: Eighty-eight patients were randomised into pulmonary rehabilitation (n=45) and control (n=43) groups. Changes in 6MWD were -33 m (95% CI -65 to -1) and -53 m (95% CI -86 to -21) in the pulmonary rehabilitation and control groups, respectively, with no statistically significant difference (mean difference, 21 m (95% CI -25 to 66), p=0.38). Changes in endurance time were significantly better in the pulmonary rehabilitation (64 s, 95% CI -42.3 to 171)) than in the control (-123 s (95% CI -232 to -13)) group (mean difference, 187 s (95% CI 34 to 153), p=0.019). INTERPRETATION: Although pulmonary rehabilitation in patients taking nintedanib did not improve 6MWD in the long term, it led to prolonged improvement in endurance time. TRIAL REGISTRATION NUMBER: UMIN000026376.

Association between airflow limitation severity and reduced bone mineral density in Japanese men.

Introduction: This study aimed to assess the association between airflow limitation (AL) severity and reduced bone mineral density (BMD) in Japanese men. Subjects and methods: This cross-sectional study included 290 subjects aged over 40 years (mean age 72.0, SD 11.6), who underwent a comprehensive health examination, including spirometry and measurement of BMD at the left femoral neck using dual-energy X-ray absorptiometry (DXA), between 2016 and 2017 at Japanese Red Cross Kumamoto Health Care Center. AL was defined as forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) of <0.7. Reversibility tests were not performed in this study. The criteria used for the AL staging were developed according to the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines. The subjects were divided into the following three groups: a control group (normal pulmonary function), GOLD Stage I group (mild AL), and GOLD Stage II-IV group (moderate-to-very severe AL). BMD was classified based on the young adult mean (YAM) as normal (88.6% ≦ YAM [-1 SD ≦]), osteopenia (70% -2.5 SD]), or osteoporosis (YAM ≦ 70% [≦ -2.5 SD]). Reduced BMD was defined as osteopenia, osteoporosis, or medication used for osteoporosis. Logistic regression analysis was used to assess the association between AL severity and the reduced BMD. Results: The prevalence of reduced BMD in subjects with moderate-to-severe AL (76.2%) was significantly higher than in those without AL (47.9%) (p=0.030). In logistic regression models adjusted for age, body mass index, pack-years, physical activity, and alcohol drinking, the risk of reduced BMD (odds ratio: 3.87; 95% confidence interval: 1.20-12.49; p=0.024) was significantly higher in subjects with moderate-to-severe AL than in those with normal pulmonary function. Conclusion: Present results suggest that reduced BMD is associated with AL severity in Japanese men.

Imidafenacin, An Orally Active Muscarinic Receptor Antagonist, Improves Pulmonary Function In Patients With Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled 3×3 Crossover Phase II Trial.

Background: Although long-acting muscarinic receptor antagonists are central to the management of chronic obstructive pulmonary disease (COPD), inhaled medicines may have technical difficulty in some patients and adherence barriers. Methods: A multicenter, randomized, double-blind, placebo-controlled 3×3 crossover Phase II trial was performed to evaluate the efficacy and safety of oral administration of the antimuscarinic agent imidafenacin in patients with COPD. Twenty-seven male COPD patients with % forced expiratory volume in 1 s (FEV1) ≥30% and <80% predicted were randomized to single oral dose of imidafenacin 0.1 mg, imidafenacin 0.2 mg, or placebo. Results: Maximum change in FEV1 with both doses of imidafenacin significantly improved from baseline to 24 hrs after administration when compared with a placebo. Area under the curve in FEV1 during 24 hrs after administration with 0.2 mg, but not 0.1 mg dose, was significantly improved when compared with a placebo, and the improvement was significantly based on dose-dependent manners. Plasma imidafenacin level was positively correlated with change in FEV1. All subjects with both doses of imidafenacin completed without moderate nor severe adverse events. Conclusion: A single oral dose of imidafenacin 0.1 mg or imidafenacin 0.2 mg may contribute to the improvement of pulmonary function with excellent safety and tolerability in patients with COPD. Trial registration: JapicCTI-121760 (Japan Pharmaceutical Information Center - Clinical Trials Information [JapicCTI]; http://www.clinicaltrials.jp/user/cteSearch_e.jsp).

A retrospective study of the tolerability of nintedanib for severe idiopathic pulmonary fibrosis in the real world.

BACKGROUND: Nintedanib is a tyrosine kinase inhibitor that has been shown to suppress progression of idiopathic pulmonary fibrosis (IPF). The efficacy and tolerability of nintedanib for IPF has been previously proven in the INPULSIS® and INPULSIS-On® trials. The aim of our study was to clarify the tolerability of nintedanib in the real world for severe IPF patients who were unable to enter the INPULSIS® and INPULSIS-On® trials. METHODS: We retrospectively investigated medical records of 8 patients with severe IPF and 14 patients with non-severe IPF who had been treated with nintedanib. The criteria to define severe IPF were forced vital capacity (FVC) of <50% predicted and/or diffusing capacity of the lung for carbon monoxide/alveolar volume (DLCO/VA) of <30% predicted or unmeasurable. Severity of adverse event was evaluated using the Common terminology criteria for each adverse event version 4.0. We compared changes in FVC and serum KL-6 level, incidence and severity of adverse events, and incidence of permanent or temporary discontinuation of nintedanib in between severe and non-severe IPF groups. RESULTS: The median treatment period was 578.5 days. The most frequent adverse event was diarrhea (73%). Only 2 patients required permanent discontinuation of nintedanib due to adverse events. There was no difference in incidence or severity of adverse events or incidence of permanent or temporary discontinuation of nintedanib in between severe and non-severe IPF groups. Among subjects, decline in FVC during 6 months post-nintedanib treatment were significantly lower than prior to treatment, but change in serum KL-6 level showed no significant difference between these 2 timepoints. CONCLUSIONS: Our study showed that nintedanib was tolerable for IPF patients who would not have been eligible for entry into previous clinical trials due to low pulmonary function. Although therapeutic strategy for severe IPF should be planned carefully, initiation of nintedanib treatment should not be dismissed solely for reasons of low pulmonary function.

Effect of manual chest wall compression in participants with chronic obstructive pulmonary disease.

[Purpose] Pulmonary rehabilitation is appropriate for most individuals with chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation consists of conditioning and exercise therapy. Conditioning includes relaxation, breathing exercises, and manual chest wall compression during expiration (CWC). CWC improves the symptoms in individuals with respiratory disease who have undergone mechanical ventilation. However, evidence supporting the effectiveness of CWC for COPD has been insufficient. This study aimed to determine physiological responses to CWC in participants with COPD. [Participants and Methods] Twenty-nine participants with COPD were included in the study. Manual CWC techniques were performed in a comfortable position chosen by the participants (sitting, forward-leaning (sitting), or semi-Fowler's). Ventilatory parameters, occlusion airway pressure (P0.1), and dyspnea were assessed using a visual analog scale and were compared before and during CWC. [Results] During manual CWC, oxygen consumption, carbon dioxide production, end-tidal carbon dioxide concentration, and dyspnea were significantly decreased; however, P0.1 was not affected. [Conclusion] Manual CWC for COPD had an immediate physiological effect, including a decrease in dyspnea that may have been facilitated by a reduced workload of the respiratory muscles. Thus, manual CWC may be effective for dyspnea by reducing oxygen consumption in the respiratory muscles.

[Efficacy and safety of levofloxacin in patients with nursing and healthcare-associated pneumonia].

Levofloxacin (LVFX) is one of respiratory quinolones with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria, and 500 mg of intravenous LVFX infusion has recently been able to use once daily based on pharmacokinetics-pharmacodynamics in Japan. So far, there had been no reports of the prospective studies evaluating efficacy and safety of LVFX in patients with nursing and healthcare-associated pneumonia (NHCAP). This study was conducted to evaluate prospectively the efficacy and safety of LVFX in patients with NHCAP categories B and C (other antibacterial agents were allowed to use with LVFX) according to Japanese guideline for NHCAP by the Japanese Respiratory Society (JRS). LVFX 500 mg was intravenously administered once daily, and the clinical efficacy and safety were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-two patients (average age was 81.2 years old, female/male was 22/40) were firstly registered and evaluated for the safety of LVFX, and eventually 54 patients were enrolled for the evaluation of clinical efficacy of LVFX. The percentage of these 54 patients aged over 65 years old was 96.3%, NHCAP category B/C was 33/21. The efficacy of LVFX in all 54 patients evaluated was 85.2% (categories B/C of NHCAP was 81.8/90.5%). In addition, the efficacies of LVFX in each pneumonia severity category by A-DROP system by JRS in NHCAP patients were 100% in mild, 86.7% in moderate, 77.8% in severe/very severe. Nine patients (2 with liver dysfunction, 6 with renal dysfunction and 1 with thrombocytopenia) out of 62 patients were reported to have possible adverse effects of LVFX. All of the patients with liver and renal dysfunctions after starting LVFX administration demonstrated mild dysfunctions and continued LVFX treatment, and these dysfunctions normalized soon after cessation of LVFX. LVFX was changed to other antibacterial agent in one patient with thrombocytopenia, and also thrombocytopenia was normalized thereafter. In conclusion, LVFX is effective and relatively safe for categories B and C in patients with NHCAP.

Development of the Japanese version of the COPD Assessment Test.

BACKGROUND: We aimed to develop the Japanese version of the COPD Assessment Test (TM) (CAT), which was recently developed in overseas countries, to measure the health status of patients with chronic obstructive pulmonary disease (COPD) and to validate its psychometric properties. METHODS: The original CAT was translated to Japanese through linguistic validation. Then, an Internet-based survey was conducted by including 301 Japanese patients with COPD who were over 40 years of age and had a history of smoking, to assess the reliability and validity of the translated CAT. RESULTS: The Japanese CAT was shown to have high internal consistency (Cronbach's α coefficient: 0.891). The assessment using the Japanese CAT was highly correlated with assessment using the COPD-specific St. George's Respiratory Questionnaire (r = 0.820). The assessment also showed correlation between the Japanese CAT and a generic health-related quality of life (QOL) questionnaire (SF-12v2). CONCLUSION: The Japanese version of the CAT has high reliability and validity, and can be expected to serve as a short and simple questionnaire for precise assessment of the health status of Japanese patients with COPD.

Validation of symptom-based COPD questionnaires in Japanese subjects.

BACKGROUND AND OBJECTIVE: Symptom-based questionnaires may be helpful in diagnosing patients with COPD. The aim of this study was to determine whether two COPD questionnaires designed in Western countries were applicable to Japanese and other Asian patients. METHODS: The participants were Japanese people aged 40 years and over. Each subject answered questions on demographics and symptoms and underwent spirometry before and after administration of a bronchodilator. Questionnaire A was designed to identify previously undiagnosed COPD and questionnaire B was designed to differentiate between COPD and asthma. RESULTS: The numbers of COPD patients who answered questionnaires A and B were 33 of 169 (19.5%) and 112 of 168 (66.7%), respectively. Comparison of the COPD group with the non-COPD group revealed a significant difference in total score in both questionnaire A and questionnaire B (both P < 0.001). The area under the receiver operating characteristic curve (AUC-ROC) for questionnaire A was 0.791. With a cut-off value of 16.5 points, the sensitivity and specificity were 0.939 and 0.404, and with a 19.5-point cut-off, sensitivity and specificity were 0.848 and 0.647, respectively. The AUC-ROC for questionnaire B was 0.765. With cut-off values of 18.5 and 24.5 points, the respective sensitivities and specificities were 0.946 and 0.393, and 0.741 and 0.607. CONCLUSIONS: A simple self-administered questionnaire can help to diagnose COPD in Japanese subjects. When these questionnaires are used in Japan, cut-off values should be set somewhat higher than in Western countries.

Efficacy and safety of formoterol in Japanese patients with COPD.

OBJECTIVE: This study evaluated the efficacy and safety of the formoterol Turbuhaler at dosages of 4.5, 9 and 18 microg bid compared with placebo in Japanese patients with COPD. METHODS: In this randomized, double-blind, placebo-controlled, multicenter study, 36 patients with a pre-bronchodilator FEV(1) value within 40 to 70% of the predicted value were randomized to receive formoterol at doses of 4.5, 9, and 18 microg bid, and placebo, for 1 week in a crossover fashion. RESULTS: The primary outcome variable, one hour post-dose FEV(1) on the last day of the one week treatment period, was significantly higher for all formoterol dosages compared with placebo (p<0.001 for all doses); adjusted g-means for formoterol 4.5, 9 and 18 microg bid, and placebo, were 1.510 L, 1.491 L, 1.520 L and 1.342 L, respectively. All three dosages of formoterol also provided significantly better improvements than placebo in the secondary variables FVC, inspiratory capacity (IC) and morning and evening PEF. Results for IC and PEF indicated a trend towards a larger improvement at higher dosages. CONCLUSION: Treatment with formoterol at dosages of 4.5, 9 and 18 microg bid showed significantly superior effects to placebo on FEV(1) in Japanese patients with COPD. The results for some of the secondary variables (IC and PEF) indicated a trend towards larger improvements at higher dosages. All dosages of formoterol were well tolerated in Japanese patients.

Effect of jaw position on forced maximum inspiratory airflow in normal Japanese subjects and in Japanese patients with sleep apnea syndrome.

PURPOSE: The purpose of this study was to evaluate whether maximum forced inspiratory airflow changes occur by changing the jaw position in Japanese normal subjects and patients with obstructive sleep apnea (OSA) classified by their craniofacial features. MATERIALS AND METHODS: The subjects included 8 male non-OSA subjects and 15 male patients with OSA whose conditions had been diagnosed with a polysomnographic recording. The OSA subjects were divided into 2 groups by means of a craniofacial (CF) score based on cephalometric variables: a high-score group (CF score > or = 4) and a low-score group (CF score < or = 3). A case-control design was utilized to assess group differences (control and 2 patient groups). Airflow changes were determined using a spirometer that assessed the velocity of airflow during forced inspiration. Maximum forced inspiratory airflow was measured in 4 positions in all patients. RESULTS: All 3 groups had a significant decrease in their maximum forced inspiratory airflow upon reclining, and there were no significant group differences regarding the magnitude of this change. The OSA subjects returned to baseline measurements more than controls when the jaw was positioned forward, as the jaw was progressively advanced in high CF score subjects. CONCLUSION: This study suggested that a protrusive jaw position allows more inspiratory airflow to occur in OSA patients compared to controls, and this was significant in the patients with a high CF score.

[A study of the long-term continuation rate of respiratory rehabilitation in a day care service].

The purpose of this study is to report on the continuation rate of an outpatient pulmonary rehabilitation service for people with pulmonary disease. In Japan, Kaigo Hoken, the long-term care insurance system for the elderly, went into effect on April 1, 2000. Under this system, a special day care service was established in our hospital in order to continue outpatient rehabilitation for the elderly with pulmonary diseases. In the present study we analyzed the continuation rate of pulmonary rehabilitation in day care for a period of 2 years. Sixty-five stable patients with chronic respiratory failure were enrolled in the program. The continuation rates for 1 year and 2 years were 67.7% and 50.8%. We found that the continuation rate was high even for patients over 75 years old. Twenty patients died during the course of the program. When these 20 cases are excluded, the continuation rates for one year and 2 years become 88.9% and 73.3%. Our day care is the first service of its kind in Japan designed specifically for chronic pulmonary disease patients. It also includes a pick-up service and social activity support. In the future, the use of social resources like our day care service for the elderly with pulmonary diseases may play an important and beneficial role in continuing outpatient rehabilitation.

[A case of allergic bronchopulmonary aspergillosis followed by diagnostic imaging for 27 years].

This patient was a 28-year-old man who had been treated with steroids for recurrent asthmatic attacks since around the age of 20. At one time the steroid therapy was discontinued and other treatments, including bronchodilator therapy and desensitization therapy, were substituted. At age 28, he first consulted our hospital due to the recurrence of attacks. We found peripheral eosinophlia and a cytologic examination revealed Curschmann spirals in his sputum. Migratory infiltrate recurred, and steroids and antibiotics were prescribed each time. A confirmed diagnosis of allergic bronchopulmonary aspergillosis was made at age 35. The patient was treated with continuous oral steroids for recurrent infiltrates. After the start of inhale steroid therapy at age 44, the frequency of attacks decreased and tapering of the oral steroids became possible. It is notable that lung tissue destruction progressed by recurrent pneumonia and emphysema extended into all portions of the lung. Furthermore, this case history is of value since it yields a series of images taken over a period of 27 years.