Patients with idiopathic pulmonary fibrosis and refractory cough have traction bronchiectasis and distorted airway architecture: a retrospective case review study.

Cough is a common and important sign/symptom in patients with idiopathic pulmonary fibrosis (IPF). However, there have been few reports focusing on cough, and the exact mechanisms for cough in patients with IPF have remained unclear. The objective of this study was to investigate the clinical features of IPF patients with refractory cough and to clarify mechanisms for cough in these patients. We retrospectively reviewed the files of patients with the diagnosis of IPF at Kanazawa University Hospital and compared the clinical features of IPF patients with refractory cough with the clinical features of IPF patients without refractory cough. Among a total of 23 patients with IPF, 10 patients (43.5%) had chronic cough. Of the ten patients, seven patients had concomitant conditions that could lead to cough. Of these seven patients, the cough of four patients was resolved after treatment of their concomitant condition. Finally, among the 23 patients there were 6 (26.1%) with refractory cough associated with IPF. Significant differences were seen between the following clinical features of IPF patients with or without refractory cough, respectively, as follows: lower body mass index (BMI; 18.8±2.5 vs. 22.8±2.5 kg/m2, P<0.01), lower forced vital capacity (FVC; 77.5%±30.4% predicted vs. 99.9%±0.53% predicted, P=0.046), and presence of traction bronchiectasis and distorted airway architecture on high-resolution computed tomography (HRCT; 83.3% vs. 11.8%, P<0.01). The difference between the proportions of patients with or without refractory cough with capsaicin cough sensitivity was not significant. Mechanical stress on the airways due to traction bronchiectasis and distorted airway architecture is a possible mechanism for cough in IPF patients.

Comparing region of interest selection and whole-field analysis for measurement of ciliary beat frequency in high-speed video analysis.

BACKGROUND: Ciliary beat frequency (CBF) is crucial in mucociliary clearance. High-speed video analysis (HSVA) is commonly used to measure CBF but lacks standardization. We compared visual observation and computer-assisted calculation using fast Fourier transformation (FFT) in freshly collected bronchial ciliary epithelial cells and cultured cells. METHODS: Bronchial epithelial cells were obtained from 12 patients who required bronchoscopic examination. Eighty-five videos of ciliary movement of freshly collected and cultured cells were recorded and used to calculate CBF using manual observation, region of interest (ROI) selection, and whole-field analysis. RESULTS: CBF measured by the ROI selection method strongly correlated with that measured using manual observation, especially in freshly collected cells. However, 27.8% of the manual observation method values were doubled in the ROI selection method, probably because a round trip of cilia was calculated as two cycles and needed to be corrected to 1/2 value. Upon increasing the number of ROIs, the results of the ROI selection method came closer to that of WFA. CONCLUSIONS: Computer-assisted calculation using FFT can aid in measuring CBF; however, current methods require visual confirmation. Further automated evaluation techniques are needed to establish more standardized and generalized CBF measurement methods using HSVA.

Prevalence and causes of chronic cough in Japan.

BACKGROUND: Chronic cough is one of the most common symptoms of respiratory diseases and can adversely affect patients' quality of life and interfere with social activities, resulting in a significant social burden. A survey is required to elucidate the frequency and treatment effect of chronic cough. However, clinical studies that cover all of Japan have not yet been conducted. METHODS: Patients who presented with a cough that lasted longer than 8 weeks and visited the respiratory clinics or hospitals affiliated with the Japan Cough Society during the 2-year study period were registered. RESULTS: A total of 379 patients were enrolled, and those who did not meet the definition of chronic cough were excluded. A total of 334 patients were analyzed: 201 patients had a single cause, and 113 patients had two or more causes. The main causative diseases were cough variant asthma in 92 patients, sinobronchial syndrome (SBS) in 36 patients, atopic cough in 31 patients, and gastroesophageal reflux (GER)-associated cough in 10 patients. The time required to treat undiagnosed patients and those with SBS was significantly longer and the treatment success rate for GER-associated cough was considerably poor. CONCLUSIONS: We confirmed that the main causes of chronic cough were cough variant asthma, SBS, atopic cough, and their complications. We also showed that complicated GER-associated cough was more likely to become refractory. This is the first nationwide study in Japan of the causes and treatment effects of chronic cough.

Practical guide for the diagnosis and management of primary ciliary dyskinesia.

OBJECTIVE: Primary ciliary dyskinesia (PCD) is a relatively rare genetic disorder that affects approximately 1 in 20,000 people. Approximately 50 genes are currently known to cause PCD. In light of differences in causative genes and the medical system in Japan compared with other countries, a practical guide was needed for the diagnosis and management of Japanese PCD patients. METHODS: An ad hoc academic committee was organized under the Japanese Rhinologic Society to produce a practical guide, with participation by committee members from several academic societies in Japan. The practical guide including diagnostic criteria for PCD was approved by the Japanese Rhinologic Society, Japanese Society of Otolaryngology-Head and Neck Surgery, Japanese Respiratory Society, and Japanese Society of Pediatric Pulmonology. RESULTS: The diagnostic criteria for PCD consist of six clinical features, six laboratory findings, differential diagnosis, and genetic testing. The diagnosis of PCD is categorized as definite, probable, or possible PCD based on a combination of the four items above. Diagnosis of definite PCD requires exclusion of cystic fibrosis and primary immunodeficiency, at least one of the six clinical features, and a positive result for at least one of the following: (1) Class 1 defect on electron microscopy of cilia, (2) pathogenic or likely pathogenic variants in a PCD-related gene, or (3) impairment of ciliary motility that can be repaired by correcting the causative gene variants in iPS cells established from the patient's peripheral blood cells. CONCLUSION: This practical guide provides clinicians with useful information for the diagnosis and management of PCD in Japan.

Bronchial Thermoplasty Attenuates Cough Reflex Sensitivity in Severe Asthma : A Single-Center Retrospective Study with 2-year Follow-up.

Despite the relatively short follow-up period in our previous study, we had reported that increased cough reflex sensitivity (CRS) may predict the efficacy of bronchial thermoplasty (BT) for treating asthma. Herein, we examined whether CRS predicts the efficacy of BT 2 years after the final BT treatment. We also investigated the influence of BT on CRS. We reviewed 10 patients 2 years after their final BT treatment. CRS, asthma-related symptoms, asthma exacerbations, and cough-related quality of life were assessed at baseline and 2 years after BT. Five patients responded positively to BT (BT responders) and their asthma control improved. No significant difference in CRS at baseline was detected between the BT responders and nonresponders. In contrast, BT responders exhibited significant improvements in CRS 2 years after BT. CRS at baseline could not predict the BT efficacy after 2 years. This is the first report demonstrating BT desensitized CRS in consecutive case series. J. Med. Invest. 70 : 271-275, February, 2023.

Primary ciliary dyskinesia with CCDC39 variants displaying specific ciliary ultrastructure and movement concordant with the genotype: A case report.

Primary ciliary dyskinesia (PCD) is a genetic disease with chronic airway infection and inflammation caused by ciliary ultrastructural defects and impairment in ciliary function. We present an adult case of PCD with compound heterozygous nonsense variants in CCDC39. The ciliary ultrastructure findings using electron microscopy and ciliary movement using high-speed video analysis matched the genotype. This is the first case report of PCD with CCDC39 variants in Japan demonstrating specific ciliary ultrastructure and movement related to the genotype.

Analysis of the clinical features of Japanese patients with primary ciliary dyskinesia.

OBJECTIVE: Primary ciliary dyskinesia (PCD) is a rare hereditary disease. Most reports of PCD in Japan are case reports, and clinical analysis has not been performed. Differences in the causative genes might affect the clinical features in different ethnic groups. The purpose of this study was to clarify the clinical features of Japanese patients with PCD. METHODS: We performed a retrospective chart review of PCD patients seen at Mie University Hospital and patients whose blood samples were sent to us for genetic analysis from 2011 to 2020. Data on the following items were collected and analyzed: age at first visit to the hospital, age at diagnosis of PCD, process of referral to our facility, chief complaint, situs status, PrImary CiliARy DyskinesiA Rule (PICADAR) score, nasal nitric oxide concentration, otoscopic findings, rhinoscopic findings, and paranasal computed tomography scan findings. RESULTS: Sixty-seven patients (24 male, 43 female) were diagnosed with PCD during the study period. Age at diagnosis ranged from 2 months to 69 years (median, 17 years). Respiratory symptoms (77%) were the most common complaint, followed by nasal (15%) and aural (8%) symptoms. Situs inversus was present in 17 (25%) cases. Only 2 cases had congenital cardiac anomalies. The mean PICADAR score was 7.3 (range, 3-14) points. Approximately 50% of tympanic membranes showed retraction, suggesting otitis media with effusion. The mean Lund-Mackay score was 12.8 (range, 7-17) points, suggesting that the radiographic findings were not always severe. There was no significant difference in the total Lund-Mackay score between patients with and without situs inversus (12.7 vs. 12.6, respectively). CONCLUSION: Situs inversus was present in 25% of Japanese PCD patients, which is much lower than observed in other countries. This is a result of differences in the major disease-causing genes. The general rule that "situs inversus is observed in approximately 50% of PCD patients" cannot be applied, at least, in Japanese PCD patients.

Fractional analysis of bronchoalveolar lavage in systemic sclerosis-associated interstitial lung disease.

BACKGROUND: The utility of bronchoalveolar lavage (BAL) in the evaluation of systemic sclerosis-associated interstitial lung disease (SSc-ILD) remains controversial. Fractional analysis of BAL (FBAL) is a technique that can analyze small airways and alveolar compartments separately and has proven informative in other ILDs. The aim of this study was to explore FBAL characteristics across the spectrum of SSc-ILD severity. METHODS: We retrospectively reviewed patients with SSc-ILD who underwent bronchoscopy with FBAL using three 50 mL aliquots of saline solution. These aliquots were analyzed separately for differential cell composition (FBAL-1, -2, and -3). We compared the FBAL cell composition to the progression of ILD and end-stages of ILD using Cox proportional hazards models. RESULTS: Sixty-eight patients with SSc-ILD were enrolled in this study. The percentage of neutrophils and eosinophils was lower in FBAL-3 compared to FBAL-1. In contrast, the percentage of macrophages and lymphocytes was higher in FBAL-3. Neutrophils in FBAL-2, -3, and the estimated total FBAL cell fraction (FBAL-total) were negatively correlated with the forced vital capacity % predicted (r=-0.420, -0.362, -0.409, respectively). Although FBAL-total was not linked to the progression and end-stage of ILD, a high percentage of neutrophils in FBAL-3 was significantly associated with the development of end-stage ILD (HR 1.093, 95% CI: 1.003-1.190). CONCLUSIONS: A higher percentage of neutrophils in FBAL-3 is correlated with development of end-stage ILD in SSc-ILD as well as mortality.

Two cases of chronic obstructive pulmonary disease evaluated by dynamic-ventilatory digital radiography for pulmonary function and assessment of treatment efficacy.

Spirometry is a crucial test used in the diagnosis and monitoring of patients with chronic obstructive pulmonary disease (COPD). Severe acute respiratory syndrome coronavirus 2 pandemic has posed numerous challenges in performing spirometry. Dynamic-ventilatory digital radiography (DR) provides sequential chest radiography images during respiration with lower doses of radiation than conventional X-ray fluoroscopy and computed tomography. Recent studies revealed that parameters obtained from dynamic DR are promising for evaluating pulmonary function of COPD patients. We report two cases of COPD evaluated by dynamic-ventilatory DR for pulmonary function and treatment efficacy and discuss the potential of dynamic DR for evaluating COPD therapy.

Chest Dynamic-Ventilatory Digital Radiography in Chronic Obstructive or Restrictive Lung Disease.

OBJECTIVE: The aim of this study was to identify the relationships between parameters obtained from dynamic-ventilatory digital radiography (DR) and ventilatory disorders. METHODS: This study comprised 273 participants with respiratory diseases who underwent spirometry and functional residual capacity measurements (104 with normal findings on spirometry as controls, 139 with an obstructive lung disorder, 30 with a restrictive lung disorder) were assessed by dynamic-ventilatory DR. Sequential chest radiography images of the patient's slow and maximum breathing were captured at 15 frames per second by a dynamic flat-panel imaging system. The system measured the following parameters: lung area at maximum inspiration divided by height (lung area_in/height), changes in tracheal diameter due to respiratory motions, rate of tracheal narrowing, diaphragmatic motion, and rate of change in lung area due to respiratory motion. Relationships between these parameters and ventilatory disorders were analyzed. RESULTS: Lung area_in/height in patients with restrictive disorders showed significant decreases. Tracheal diameter change and tracheal narrowing rate in patients with obstructive disorders were significantly increased compared to both the control participants and patients with restrictive disorders. Patients with obstructive disorders and patients with restrictive disorders showed decreased diaphragmatic motion and lung area change rate. With the restrictive disorders as references, the area under the curve (AUC), sensitivity and specificity of lung area_in/height were 0.88, 0.77, and 0.88, respectively. With the obstructive disorders as references, the AUC, sensitivity and specificity of tracheal narrowing rate were 0.67, 0.53 and 0.81, respectively. CONCLUSION: Dynamic-ventilatory DR shows potential as a method for the detection and evaluation of ventilatory disorders in patients with respiratory diseases.

Late-onset programmed cell death protein-1 inhibitor-induced pneumonitis after cessation of nivolumab or pembrolizumab in patients with advanced non-small cell lung cancer: a case series.

Awareness of the immune-related adverse event of programmed cell death protein-1 (PD-1) inhibitor-induced pneumonitis is important. Herein, we report the clinical course of 3 patients suspected to have PD-1 inhibitor-induced pneumonitis after cessation of PD-1 inhibitor treatment. In case 1, a 62-year-old man was diagnosed with stage IVA adenocarcinoma. Nivolumab monotherapy was prescribed as second-line therapy and later discontinued due to financial reasons. Seven months after the final administration of nivolumab, the patient developed what we diagnosed as nivolumab-induced pneumonitis. The patient was immediately prescribed prednisolone (1 mg/kg p.o. daily), and the pneumonitis resolved after 1.5 months. In case 2, a 68-year-old man was diagnosed with stage IVB squamous cell carcinoma. Nivolumab monotherapy was prescribed as fourth-line therapy. After the second administration of nivolumab, the patient developed what we diagnosed as nivolumab-induced pneumonitis; nivolumab was discontinued, and the patient was immediately prescribed prednisolone (1 mg/kg p.o. daily). Eight months after the final administration of nivolumab, the patient again developed nivolumab-induced pneumonitis. The pneumonitis resolved without additional medication. In case 3, a 69-year-old man was diagnosed with stage IVB adenocarcinoma. Pembrolizumab monotherapy was initiated as sixth-line therapy, and it was discontinued after 4 cycles due to disease progression. Four months after the final dose of pembrolizumab, the patient developed what we diagnosed as pembrolizumab-induced pneumonitis. The patient immediately received a high intravenous dose of methylprednisolone (1,000 mg per day for three days). The pneumonitis and respiratory failure progressed, and he died 8 weeks after the onset of the pneumonitis. We report pneumonitis after discontinuation of ICIs in 3 patients. We confirm that, although uncommon, PD-1 inhibitor-induced irAEs can develop after treatment discontinuation. Further accumulation of cases and clarification of the clinical features of patients with irAEs, such as the time of onset, imaging findings, and treatment outcomes are needed.

Methacholine-induced cough as an indicator of bronchodilator-responsive cough.

BACKGROUND: Cough variant asthma (CVA) is the most common cause of chronic cough and responds well to bronchodilator therapy. Previous studies on methacholine -induced cough have shown that heightened cough response due to bronchoconstriction is a feature of CVA. The aim of this study was to assess Mch-induced cough as an indicator of bronchodilator-responsive cough (BRC). METHODS: This was a single-center retrospective study of prolonged/chronic cough cases who underwent evaluation via spirometry, FeNO and bronchial challenge testing using Mch and capsaicin (C5). Resultant bronchoconstriction after Mch challenge was assessed by flow-volume curves measuring the expiratory flow of the partial flow-volume curve 40% above residual volume (PEF40) and FEV1. BRC was defined as a decrease in cough with bronchodilator therapy by 30% or more on a visual analog scoring scale. RESULTS: Of the 100 patients evaluated, 63 were diagnosed with BRC. Mch-induced cough at a decrease in PEF40 of 35% (PC35-PEF40) was predictive of BRC on AUROC analysis with an AUC of 0.82 (95% CI 0.73-0.90) and cut-off of 24. The AUC for C5, FeNO and PC20-FEV1 were 0.65, 0.47, and 0.58, respectively. CONCLUSION: Compared to C5, FeNO and PC20-FEV1, Mch-induced cough better supports a diagnosis of BRC.

Dynamic-Ventilatory Digital Radiography in Air Flow Limitation: A Change in Lung Area Reflects Air Trapping.

OBJECTIVE: The aim of this study was to determine the utility of dynamic-ventilatory digital radiography (DR) for pulmonary function assessment in patients with airflow limitation. METHODS: One hundred and eighteen patients with airflow limitation (72 patients with lung cancer before surgery, 35 patients with chronic obstructive pulmonary disease [COPD], 6 patients with asthma, and 5 patients with asthma-COPD overlap syndrome) were assessed with dynamic-ventilatory DR. The patients were instructed to inhale and exhale slowly and maximally. Sequential chest X-ray images were captured in 15 frames per second using a dynamic flat-panel imaging system. The relationship between the lung area and the rate of change in the lung area due to respiratory motion with respect to pulmonary function was analyzed. RESULTS: The rate of change in the lung area from maximum inspiration to maximum expiration (Rs ratio) was associated with the RV/TLC ratio (r = 0.48, p < 0.01) and the percentage of the predicted FEV1 (r = -0.33, p < 0.01) in patients with airflow limitations. The Rs ratio also decreased in an FEV1-dependent manner. CONCLUSION: The rate of change in the lung area due to respiratory motion evaluated with dynamic DR reflects air trapping. Dynamic DR is a potential tool for the comprehensive assessment of pulmonary function in patients with COPD.

Histopathological Type of Lung Cancer and Underlying Driver Mutations in Patients with Chronic Obstructive Pulmonary Disease (COPD) versus Patients with Asthma and COPD Overlap: A Single-Center Retrospective Study.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) increases the risk of lung cancer. The relationships between COPD and Asthma COPD Overlap (ACO), and between the histopathological types of lung cancer and driver mutations remain unclear and need further study. The aim of this retrospective study was to examine the relationships between the histopathological type, frequency of epidermal growth factor receptor (EGFR) driver mutations, and anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements in the lung cancers of patients with COPD and ACO. MATERIALS AND METHODS: Patients with pure COPD (n=198) or ACO (n=318) who were admitted to our hospital were reviewed retrospectively. RESULTS: Lung cancers were identified in 43 (21.7%) patients with pure COPD and 54 (17.0%) patients with ACO. The following lung cancers types were observed: patients with pure COPD had 19 (44.2%) adenocarcinomas, 13 (30.2%) squamous cell lung carcinomas (SCC), 8 (18.6%) small cell lung carcinomas (SCLC); patients with ACO had 23 (42.6%) adenocarcinomas, 23 (42.6%) SCC, 2 (3.70%) SCLC. SCLC was significantly more prevalent in patients with pure COPD (p<0.05) than in those with ACO. Differences between the numbers of other histological types of lung cancer and the numbers of driver mutations in the 2 groups of patients were not significant. CONCLUSION: The differences in the rate of lung cancer and prevalence of EGFR driver mutations between the patients with pure COPD and those with ACO were not significant.

Copy number variation in DRC1 is the major cause of primary ciliary dyskinesia in the Japanese population.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by functional impairment of cilia throughout the body. The involvement of copy number variation (CNV) in the development of PCD is largely unknown. METHODS: We examined 93 Japanese patients with clinically suspected PCD from 84 unrelated families. CNV was examined either by exome sequencing of a PCD gene panel or by whole-exome sequencing (WES). The identified alterations were validated by PCR and Sanger sequencing. Nasal ciliary ultrastructure was examined by electron microscopy. RESULTS: Analysis of CNV by the panel or WES revealed a biallelic deletion in the dynein regulatory complex subunit 1 (DRC1) gene in 21 patients, which accounted for 49% of the PCD patients in whom a disease-causing gene was found. Sanger sequencing of the PCR product revealed a 27,748-bp biallelic deletion including exons 1-4 of DRC1 with identical breakpoints in all 21 patients. The ciliary ultrastructure of the patients with this CNV showed axonemal disorganization and the loss or gain of central microtubules. CONCLUSION: The deletion of DRC1 is the major cause of PCD in Japan and this alteration can cause various ciliary ultrastructural abnormalities.

Repeated bronchoconstriction attenuates the cough response to bronchoconstriction in naïve guinea pigs.

BACKGROUND: Cough variant asthma (CVA) is recognized as a precursor of bronchial asthma (BA). However, the cough response to bronchoconstriction differs between these similar diseases. Repeated bronchoconstriction and the resulting imbalance of endogenous lipid mediators may impact the cough response. METHODS: We investigated the influence of repeated bronchoconstriction on the cough response to bronchoconstriction using naïve guinea pigs. Bronchoconstriction was induced for 3 consecutive days and changes in the cough response and lipid mediators, such as PGE2, PGI2, and cysteinyl-LTs (Cys-LTs), in BAL fluid (BALF) were assessed. We investigated the effect of endogenous PGI2 on the cough response by employing a PGI2 receptor antagonist. In order to investigate the cough response over a longer period, we re-evaluated the cough response 2 weeks after repeated bronchoconstriction. RESULTS: The number of coughs induced by bronchoconstriction were significantly decreased by repeated bronchoconstriction. The levels of PGE2, PGI2, and Cys-LTs, and the ratio of PGI2/PGE2 were significantly increased, following repeated bronchoconstriction. This decrease in the cough response was suppressed by pretreatment with a PGI2 receptor antagonist. Two weeks after repeated bronchoconstriction, the cough response returned to the same level as before repeated bronchoconstriction along with a concomitant return of lipid mediators, such as PGE2, PGI2, and Cys-LTs and the ratio of PGI2/PGE2. CONCLUSIONS: Our results suggest that repeated bronchoconstriction and the resulting imbalance of endogenous lipid mediators contribute to the difference in cough responses to bronchoconstriction in CVA and BA.

The prevalence and clinical features of asthma-COPD overlap (ACO) definitively diagnosed according to the Japanese Respiratory Society Guidelines for the Management of ACO 2018.

Background Asthma-COPD overlap (ACO) is a disease that shares clinical features of both asthma and COPD. The purpose of this study is to investigate the prevalence and clinical features of ACO. Methods We retrospectively reviewed data for 170 patients with persistent airflow limitation and diagnosed them according to "The Japanese Respiratory Society Guidelines for the Management of ACO 2018". Results Of the 170 patients, 111 were diagnosed as follows : COPD (74 patients, 66.6%), ACO (34 patients, 30.6%), and asthma (3 patients, 2.8%). There was no significant difference in clinical features between ACO and COPD patients. The following pulmonary function tests were significantly lower in ACO than in COPD patients : forced expiratory volume in 1 second/forced vital capacity, peak expiratory flow, maximal mid-expiratory flow, and the maximum expiratory flow at 50%and75%. The following respiratory impedance parameters were significantly higher in ACO than in COPD patients : respiratory resistance (Rrs) at 5 Hz (R5), Rrsat 20 Hz (R20), R5-R20, and low-frequency reactance area. Conclusions About 30% of patients with persistent airflow limitation were diagnosed with ACO. ACO patients had lower lung function and higher respiratory impedance compared with COPD patients. J. Med. Invest. 66 : 157-164, February, 2019.

Increased Cough Receptor Sensitivity to Capsaicin Predicts a Positive Bronchial Thermoplasty Response: A Single-center Retrospective Study.

BACKGROUND: Bronchial thermoplasty (BT) is a novel bronchoscopic therapy for severe uncontrolled asthma unresponsive to standard pharmacological treatments, including inhaled corticosteroids and long-acting beta-2 agonists. Although several studies have shown that BT improves asthma control, the optimal predictors of BT response remain unknown. PATIENTS AND METHODS: We reviewed 10 consecutive asthma patients treated with BT at Kanazawa University Hospital between January 2016 and March 2018 and attempted to identify factors that correlated with a positive BT response. RESULTS: All patients had the most severe persistent asthma according to the 2017 Japanese guidelines for adult asthma and were uncontrolled despite adequate treatments including high-dose inhaled corticosteroids and long-acting beta-2 agonists. Six patients had significant improvement in asthma control evaluated with the Asthma Control Questionnaire-6. Eight patients showed a significant improvement in asthma-specific health-related quality of life evaluated with the Asthma Quality of Life Questionnaire. The number of severe asthma exacerbations decreased in 6 patients. The maintenance dose of oral corticosteroids decreased in 1 patient. There were no severe adverse events related to the procedure. Six patients showed a positive BT response, and all 4 patients with increased cough receptor sensitivity to capsaicin responded to BT. No other factors, including age, smoking status, body mass index, age of asthma onset, disease duration, blood eosinophil count, total serum immunoglobulin E, prebronchodilator forced expiratory volume in 1 second, reversibility to beta-2 agonist, or fractional exhaled nitric oxide, were associated with a positive BT response. CONCLUSION: Increased cough receptor sensitivity to capsaicin may predict a positive BT response.

A Single Institution Retrospective Study of the Clinical Efficacy of Tiotropium Respimat in Never-Smoking Elderly Asthmatics with Irreversible Airflow Limitation.

OBJECTIVE: In Japan, most asthma deaths occur among the elderly. We should improve the control of asthma in elderly patients to reduce the number of deaths due to asthma. This retrospective study aimed to evaluate the efficacy of tiotropium RespimatⓇ (Tio-Res) in symptomatic, never-smoking, elderly asthmatics with irreversible airflow limitation despite the use of high-dose inhaled corticosteroids (ICS) plus long-acting ß2-adrenoceptor agonists (LABA). METHODS: The Asthma Control Test™ (ACT), pulmonary function tests, morning and evening peak flow (mPEF, ePEF, respectively, evaluated with an ASSESS® peak flow meter), and respiratory impedance (assessed with MostGraph®) were measured before and after a minimum of one year of Tio-Res 5 µg/day administration. Sixteen symptomatic, never-smoking asthmatics, aged 75 or over with irreversible airflow limitation despite the use of high-dose ICS plus LABA, were analyzed. RESULTS: All patients were female (mean age, 81.6 years). Tio-Res led to statistically significant improvements in the total ACT score (19.9 to 23.6), FVC and FEV1 (1.97 to 2.14 L and 1.13 to 1.23 L, respectively), and mPEF and ePEF (229.9 to 253.8 L/min and 259.8 to 277.4 L/min, respectively). Tio-Res also resulted in statistically significant improvements in respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20), R5-R20, low-frequency reactant indices at 5 Hz (X5), resonant frequency (Fres) and low-frequency reactance area (ALX). CONCLUSIONS: Our retrospective study suggests that Tio-Res improves symptoms, pulmonary function, and respiratory impedance in symptomatic asthmatics aged 75 or over with irreversible airflow limitation despite the use of high-dose ICS plus LABA.