Predictors of exacerbation in Japanese patients with severe asthma: Analysis of the severe asthma research program (Okayama-SARP) cohort.

BACKGROUND: Because exacerbation of severe asthma decreases patients' quality of life, this study aimed to identify predictive factors for asthma exacerbation. METHODS: Japanese patients with severe asthma requiring treatment according to the Global Initiative for Asthma (GINA) guidelines ≥ Step 4 between January 2018 and August 2021 were prospectively enrolled and followed up for one year at facilities participating in the Okayama Respiratory Disease Study Group (Okayama Severe Asthma Research Program). RESULTS: A total of 85 patients (29 men and 56 women) were included. The median age was 64 (interquartile range [IQR], 51-72) years. Treatment according to GINA Steps 4 and 5 was required in 29 and 56 patients, respectively, and 44 patients (51.8%) were treated with biologics. The median peripheral-blood eosinophil count, fractional exhaled nitric oxide, IgE level, and percent predicted FEV1 (%FEV1) at enrollment were 204 (IQR, 49-436)/µL, 28 (IQR, 15-43) ppb, 172 (IQR, 56-473) IU/mL, and 80.0 (IQR, 61.1-96.1) %, respectively. Exacerbation during the previous year, asthma control test (ACT) score <20, %FEV1 <60%, and serum IL-10 level >6.7 pg/mL were associated with exacerbation during the observation period. CONCLUSIONS: Exacerbation during the previous year, low ACT score, and low %FEV1 were predictive factors of future exacerbation, even in a cohort with >50% of patients treated with biologics. Furthermore, high serum IL-10 levels might be a new predictive factor.

Switching to Dupilumab from Other Biologics without a Treatment Interval in Patients with Severe Asthma: A Multi-Center Retrospective Study.

BACKGROUND: Dupilumab is a fully humanized monoclonal antibody that blocks interleukin-4 and interleukin-13 signals. Several large clinical trials have demonstrated the efficacy of dupilumab in patients with severe asthma. However, few studies have examined a switch to dupilumab from other biologics. METHODS: This retrospective, multi-center observational study was conducted by the Okayama Respiratory Disease Study Group. Consecutive patients with severe asthma who were switched to dupilumab from other biologics without a treatment interval between May 2019 and September 2021 were enrolled. Patients with a treatment interval of more than twice the standard dosing interval for the previous biologic prior to dupilumab administration were excluded. RESULTS: The median patient age of the 27 patients enrolled in this study was 57 years (IQR, 45-68 years). Eosinophilic chronic rhinosinusitis (ECRS)/chronic rhinosinusitis with nasal polyp (CRSwNP) was confirmed in 23 patients. Previous biologics consisted of omalizumab (n = 3), mepolizumab (n = 3), and benralizumab (n = 21). Dupilumab significantly improved FEV1 (median improvement: +145 mL) and the asthma control test score (median improvement: +2). The overall response rate in patients receiving dupilumab for asthma as determined using the Global Evaluations of Treatment Effectiveness (GETE) was 77.8%. There were no significant differences in the baseline characteristics of the GETE-improved group vs. the non-GETE-improved group. ECRS/CRSwNP improved in 20 of the 23 patients (87.0%). Overall, 8 of the 27 patients (29.6%) developed transient hypereosinophilia (>1500/µL), but all were asymptomatic and able to continue dupilumab therapy. CONCLUSIONS: Dupilumab was highly effective for the treatment of severe asthma and ECRS/CRSwNP, even in patients switched from other biologics without a treatment interval.

[LOWER RESPIRATORY TRACT SCREENING USING FRACTIONAL EXHALED NITRIC OXIDE IN PATIENTS WITH EOSINOPHILIC CHRONIC RHINOSINUSITIS].

BACKGROUND: It is known that eosinophilic chronic rhinosinusitis is often associated with adult-onset bronchial asthma, and undiagnosed bronchial asthma is also known to be included. The purpose of this study is to screen patients with eosinophilic chronic rhinosinusitis using fractional exhaled nitric oxide, and to examine its usefulness in detecting undiagnosed bronchial asthma. METHODS: We retrospectively examined the data of patients with eosinophilic chrnoic rhinosinusitis who underwent surgical treatment at Kagawa University from April 2015 to July 2022. Patients were included if they received examinations of fractional exhaled nitric oxide and spirometry before surgical treatment. RESULTS: Of the 127 subjects, 52 had no history of treatment or diagnosis of bronchial asthma at the initial consultation. Among them, 15 patients who had high fractional exhaled nitric oxide value were diagnosed with bronchial asthma by the respiratory medicine department. Comorbid of bronchial asthma was eventually increased to 70.9% even though it was 59.1% at initial consultation. CONCLUSION: A certain number of patients with eosinophilic chronic rhinosinusitis have undiagnosed bronchial asthma, which can be difficult to detect with basic examination alone therefore fractional exhaled nitric oxide is useful as an additional screening examination.

Intravenous immunoglobulin for acute exacerbation of fibrotic idiopathic interstitial pneumonias.

BACKGROUND AND AIM: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a fatal condition with no established treatment. Intravenous immunoglobulin (IVIG) is a unique therapy with both anti-inflammatory and anti-infective effects. Therefore, we hypothesized that IVIG may have a positive effect on AE of interstitial pneumonia. This study aimed to determine the effect of IVIG in patients with AE of fibrotic idiopathic interstitial pneumonias (IIPs), including IPF. METHODS: We retrospectively analyzed consecutive patients who were diagnosed with AE of fibrotic IIPs and treated with pulse corticosteroid therapy (methylprednisolone 500-1000 mg/day for 3 days) between April 2018 and May 2021 at Kagawa Rosai Hospital and KKR Takamatsu Hospital. RESULTS: This study included 52 patients with AE of fibrotic IIPs (IPF,41; fibrotic IIPs other than IPF,11). Thirteen patients received IVIG (5 g/day for 3-5 days) concurrently with pulse corticosteroid therapy. The remaining 39 patients were assigned to the control group. The survival rate on day 90 was significantly higher in the IVIG group than that in the control group (76.9% vs. 38.5%, p = 0.02). IVIG administration (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.02-0.69; p = 0.02) and C- reactive protein (OR, 1.19; 95% CI, 1.06-1.33, p < 0.01) were independently associated with 90-day mortality. CONCLUSIONS: The results indicate that administration of IVIG may improve the survival of patients with AE of fibrotic IIPs. We are now conducting a prospective study to confirm the effect of IVIG on AE of IPF since May 2022 (jRCT1061220010).

Obstructive Sleep Apnea Syndrome as a Potential Cause of Nocturia in Younger Adults.

OBJECTIVES: To investigate the impact of age on the relationship between obstructive sleep apnea syndrome (OSAS), nocturia, and other lower urinary tract symptoms (LUTSs). METHODS: This was a secondary analysis study based on data derived from a previously conducted prospective observational cohort study on OSAS and nocturia. We analyzed 90 subjects who were suspected of having OSAS. Prior to polysomnography, we assessed International Prostate Symptom Score-Quality of Life scores, Overactive Bladder Symptom Scores, and International Consultation on Incontinence Modular Questionnaire-Nocturia Quality of Life scores to evaluate LUTSs. Nocturnal urine volume, night-time frequency, and night-time urine electrolyte content were measured during polysomnography. Patients were divided into groups according to age and OSAS severity determined using apnea-hypopnea index (AHI) scores. Young patients were those aged <65 years and elderly patients, ≥65 years. A multiple linear regression with multiple imputations was performed to examine the association of night-time frequency with demographic, polysomnographic, and clinical characteristics. RESULTS: In young patients, night-time frequency was significantly associated with nocturnal urine volume, AHI score, and total IPSS. However, night-time frequency in elderly subjects was not associated with demographic and polysomnographic characteristics. In order to compare the severity of OSAS, night-time frequency and urinary sodium content significantly increased only in young patients (P = .007 and .004, respectively). CONCLUSION: OSAS is a strong candidate of causative factor for nocturia in younger individuals. When a younger patient complains nocturia without any urological disorders, OSAS should be kept in mind as a potential cause of nocturia.

Locomotive Syndrome is a Risk Factor for the Dropout of Continuous Positive Airway Pressure Treatment in Patients with Obstructive Sleep Apnea Syndrome.

Objective: The purpose of this study was to investigate the risk factors linked to patient dropout from continuous positive airway pressure (CPAP) therapy for the treatment of obstructive sleep apnea syndrome (OSAS). Methods: This study included 1191 patients with OSAS at baseline assessment, who were followed for 3 years. We evaluated clinical parameters, indicators related to OSAS treatment, exercise habits and the presence of locomotive syndrome (LS). LS was evaluated by a 'loco-check', as established by the Japanese Orthopedic Association. The OSAS patients were categorized at baseline as belonging to an 'LS group' or a 'non-LS group', and clinical parameters were compared. Results: Eighty-six patients (7.2%) dropped out of CPAP therapy during the 3 year follow-up period. The dropout rate of the LS group was significantly higher than that of the non-LS group. Using a Cox-proportional hazard model, the LS, old age and poor compliance were determined to be significant risk factors for dropping out of CPAP therapy. The hazard ratios (95% CI) of LS, elderly people and poor CPAP compliance were 2.11 (1.31-3.48), 1.80 (1.11-2.94) and 1.61 (1.04-2.47), respectively. Conclusion: LS may be the critical risk factor for dropping out of CPAP therapy among patients with OSAS.

Asthma mortality based on death certificates: A demographic survey in Kagawa, Japan.

BACKGROUND: We aimed to determine the reasons for the high rate of asthma mortality in Kagawa Prefecture, Japan, by analyzing death certificates. METHODS: We analyzed the death certificates between 2009 and 2011 in a demographic survey. Of 1187 patients with documented disease names suggesting bronchial asthma, analysis was performed on 103 patients in whom the cause of death was classified as asthma based on ICD-10 Codes. The patients were then classified into the following 4 groups: asthma death, asthma-related death, non-asthma death, and indistinguishable death. Based on this classification, consistency between ICD-10-based asthma death and asthma/asthma-related deaths was examined for each age group as well as for the site of death. RESULTS: Of 103 asthma deaths based on the ICD-10 classification, 30 (29%) were classified as asthma death, 44 (43%) as asthma-related death, 16 (16%) as non-asthma death, and 13 (13%) as indistinguishable death. Asthma death based on our classification correlated with that of ICD-10-based classification as a cause of death in patients younger than the median age (87 years), but correlation was not observed in patients aged older than 87 years. Deaths occurred outside the hospital in 45% of patients, and many ICD-10-based deaths reported at nursing homes and geriatric health care facilities were classified as non-asthma deaths in this survey. CONCLUSION: Re-examination of the death certificate revealed that asthma deaths were reported incorrectly on the death certificates of elderly patients who died outside the hospital.

Relationship of locomotive syndrome with health-related quality of life among patients with obstructive sleep apnea syndrome.

[Purpose] This study aimed to examine the prevalence of locomotive syndrome among patients with obstructive sleep apnea syndrome (OSAS) using the "loco-check" recently developed by the Japanese Orthopedic Association, and to compare health-related quality of life (HRQOL) among patients with and without locomotive syndrome. [Subjects and Methods] This cross-sectional study evaluated 1,195 outpatients with OSAS (1,030 males and 165 females). Locomotive syndrome was evaluated using the Japanese Orthopedic Association's "loco-check". HRQOL and psychological distress were evaluated using the EuroQol 5-dimensional (EQ-5D) and 6-item Kessler questionnaires. [Results] Locomotive syndrome was detected in 578 patients (48.4%), including 398 males (38.6% of males) and 119 females (70.3% of females). Patients with OSAS and locomotive syndrome had significantly lower EQ-5D scores, compared to patients without locomotive syndrome. Multiple regression analysis revealed that HRQOL among patients with OSAS was independently associated with locomotive syndrome, age, gender, body mass index, apnea hypopnea index, the Japanese version of the Epworth Sleepiness Scale score, and exercise habits. [Conclusion] The prevalence of locomotive syndrome was thought to be comparatively high in patients with OSAS, and locomotive syndrome was associated with lower HRQOL, even after adjusting for confounding factors. Prevention or management of locomotive syndrome may be beneficial for improving HRQOL among patients with OSAS.

Problems of elderly patients on inhalation therapy: Difference in problem recognition between patients and medical professionals.

BACKGROUND: There is no systematic analysis to identify problems involved with instruction on inhalation therapy for elderly patients. We conducted a nationwide questionnaire survey for patients and medical professionals. METHODS: A questionnaire survey was conducted of adult patients on inhaled drugs (ages 18-92 years, 820 individuals) and medical professionals (pharmacists or nurses) who provided instruction on inhalation therapy to these patients in 23 institutions in Japan to investigate the technique and the level of understanding (knowledge) of the inhalation therapy. Changes in the recognition of performance of inhalation technique and inhalation knowledge with increasing age were analyzed. RESULTS: According to patients' subjective assessment, there was no deterioration in the performance of the inhalation technique or loss of the knowledge with increasing age. On the other hand, medical professionals' objective assessment revealed a significant loss of both inhalation technique and knowledge with increasing age. Not many elderly patients noticed their own problems themselves, revealing a great perception gap between elderly patients and medical professionals. Thus, there was concern that patients would unconsciously practice the inhalation procedure improperly. On the other hand, in comparison with non-elderly patients, elderly patients were less resistant to continuation of therapy, suggesting that they would be more likely to accept instruction on inhalation therapy. CONCLUSIONS: Elderly patients are apt to assume that they "understand well", therefore, in order to recognize and close the perception gap between elderly patients and medical professionals, it is necessary to provide them with more aggressive (frequent) instructions on inhalation therapy.

Effect of the continuous positive airway pressure on the nocturnal urine volume or night-time frequency in patients with obstructive sleep apnea syndrome.

OBJECTIVE: To evaluate the effect of continuous positive airway pressure (CPAP) treatment on nocturnal urine volume, night-time urine frequency, and quality of life (QOL) in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Ninety-eight participants with suspicious diagnosis of OSAS were prospectively enrolled in this study. Before polysomnography, measurement of the International Prostate Symptom Score-QOL score, the Overactive Bladder Symptom score (OABSS), the International Consultation on Incontinence Modular Questionnaire-Nocturia QOL were carried out to evaluate the lower urinary tract symptoms. During polysomnography, nocturnal urine volume and night-time urine frequency were recorded, and the concentrations of electrolytes in urine were determined. OSAS was confirmed in 92 patients, and 63 patients started to undergo CPAP treatment. Change in lower urinary tract symptoms-related QOL was assessed 1 month after CPAP treatment in 51 patients. Additionally, urine was collected at the time of CPAP titration in 25 patients. RESULTS: CPAP treatment significantly improved night-time frequency, which resulted in the improvement of total IPSS and QOL score. The night-time frequency questionnaire in OABSS similarly decreased, although total OABSS scores were not significantly improved. The International Consultation on Incontinence Modular Questionnaire-Nocturia QOL showed no significant changes after CPAP treatment. In addition to the night-time frequency, nocturnal urine volume and urine electrolyte contents significantly decreased after CPAP treatment. CONCLUSION: CPAP treatment decreases night-time urine frequency by reducing nocturnal urine volume and improves QOL in OSAS patients.

[A case of idiopathic bronchiolitis obliterans accompanied with pneumothorax and pulmonary atypical mycobacteriosis].

A 22-year-old man was urgently admitted for pneumothorax. He continued complaining of exertional dyspnea and dry cough after the pneumothorax healed. About three months later, an atypical pulmonary mycobacteriosis by mycobacterium kansasii was identified. Exertional dyspnea increased after chemotherapy was administered, and the patient was readmitted because of difficulty in daily life activities. Chest radiographs and CT scans showed bilateral pulmonary hyperinflation and a narrowed heart shadow. There was also marked combined ventilatory impairment, as identified by a respiratory function test. Furthermore, the histological findings of surgically removed lung tissue revealed accumulation of lymphocytes in the wall of a small bronchus. Idiopathic bronchiolitis obliterans was diagnosed from the clinical course and clinical findings. The patient is now being monitored and is awaiting lung transplantation.