Clinical features of relapsed connective tissue disease-associated organizing pneumonia.

BACKGROUND: Organizing pneumonia (OP) is recognized as a nonspecific lung injury response characterized histopathologically by the presence of intra-alveolar buds of granulation tissue. Most OP patients show excellent responses to corticosteroids, but relapse is frequently seen when corticosteroids are tapered or discontinued. Although several factors associated with relapse have been reported in cryptogenic OP (COP), the clinical features and risk factors associated with relapse in connective tissue disease-associated OP (CTD-OP) have yet to be fully understood. METHODS: We retrospectively reviewed data on 47 CTD-OP patients. We investigated the frequency of relapse and compared the clinical data between CTD-OP with and without relapse to clarify the risk factors for relapse. RESULTS: Eleven (23.4%) CTD-OP patients had relapses of OP during the study. In the multivariate analysis, no CTD treatment at OP diagnosis [O.R. 11.920, p = 0.012] and partial remission after steroid treatment [O.R. 35.944, p = 0.045] were independent risk factors for relapse. Among rheumatoid arthritis-associated OP (RA-OP) patients, partial remission after steroid treatment [O.R. 16.151, p = 0.047] and age at OP diagnosis [O.R. 0.899, p = 0.045] were independent risk factors for relapse. Most of the relapsed OP patients who were on no medication at OP diagnosis later developed CTD. CONCLUSION: CTD-OP patients with residual disease on HRCT after treatment and who had OP diagnosis preceding CTD diagnosis were more likely to have an OP relapse. During the clinical course of relapsed OP patients, it is necessary to pay attention to the onset of CTD.

Acute exacerbation in antineutrophil cytoplasmic antibody-associated interstitial lung disease: Clinical features and risk factors.

BACKGROUND: Acute exacerbation (AE) is a life-threatening clinical event that occurs during the clinical course of idiopathic pulmonary fibrosis (IPF). Several studies have reported that AE also occurs in interstitial lung disease (ILD) other than IPF. However, the incidence, clinical features, risk factors for AE, and major causes of death in antineutrophil cytoplasmic antibody (ANCA)-associated ILD (ANCA-ILD) patients have not been well established. METHODS: We retrospectively reviewed the data of 54 ANCA-ILD patients and 304 IPF patients. We investigated the frequency of AE, post-AE prognoses, risk factors for AE, and major causes of death in ANCA-ILD patients. We also compared the data of ANCA-ILD with that of IPF. RESULTS: Fourteen (25.9%) ANCA-ILD patients and 84 (27.6%) IPF patients developed AE. The median survival times (MSTs) after AE in ANCA-ILD and IPF patients were 35.5 and 60 days, respectively (p = 0.588, log-rank test). In a multivariate analysis, the percentage of predicted forced vital capacity (%FVC) [O.R. 0.750 (95% CI 0.570, 0.986), p < 0.01] and serum C-reactive protein (CRP) [O.R. 2.202 (95% CI 1.037, 4.674), p < 0.01] were independent risk factors for AE. AE was the most frequent cause of death in ANCA-ILD and IPF patients. CONCLUSION: ANCA-ILD patients could develop AE, and the frequency of AE in ANCA-ILD is similar to that in IPF. AE is the most frequent cause of death in ANCA-ILD patients. A low %FVC and a high serum CRP level were independent predictive factors for AE in ANCA-ILD. The prognosis after AE in ANCA-ILD was poor, as it was in IPF.

Impact of extrapulmonary comorbidities on physical activity in chronic obstructive pulmonary disease in Japan: A cross-sectional study.

Physical activity, which can be affected by airflow limitation and extrapulmonary comorbidities, has been reported to be reduced in patients with chronic obstructive pulmonary disease, and reduced physical activity is associated with higher risks of exacerbation and mortality. The aim of the present study is to elucidate the comprehensive effect of extrapulmonary comorbidities on physical activity in Japanese patients with chronic obstructive pulmonary disease, of which evidence is lacking. We conducted a cross-sectional study with a series of tests, including lung function, physical activity, symptom scores, and parameters for comorbidities. Sixty outpatients with stable disease were enrolled, and the relationship between the parameters and physical activity was evaluated. Physical activity was assessed over 7 consecutive days using a triaxial accelerometer, which records total daily energy expenditure, step count, and walking time. Cardiovascular status was assessed via echocardiography, and pulmonary artery pressure was estimated using Doppler sonography. As to mental status, depression and anxiety were assessed using the Self-Rating Depression Scale and State-Trait Anxiety Inventory, respectively. Physical activity level was significantly correlated with step count, walking time, body mass index, lean body mass index, lung function, pulmonary artery pressure, depression, anxiety, and serum total cholesterol level. In a median regression model analysis, low lung function, low lean body mass index, depression, and low serum total cholesterol level were independently associated with decreased physical activity level. These findings suggest that physical inactivity is affected by multiple extrapulmonary factors, including skeletal muscle dysfunction, depressive symptoms, and nutritional state, in Japanese patients with chronic obstructive pulmonary disease.

Clinical features of acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: Comparison with idiopathic pulmonary fibrosis.

BACKGROUND: Several studies have reported that acute exacerbation (AE), which occurs during the clinical course of idiopathic pulmonary fibrosis (IPF), also occurs in rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the incidence, clinical features, and risk factors for AE, a major cause of death of RA-ILD patients, and the differences in clinical aspects of AE between RA-ILD and IPF have yet to be fully understood. METHODS: We retrospectively reviewed data on 149 RA-ILD patients and 305 IPF patients. We investigated the frequency of AE and compared the clinical data between RA-ILD with and without AE to clarify the risk factor for AE. We also compared the post-AE prognosis and cause of death between RA-ILD and IPF patients. RESULTS: Twenty-seven (18.1%) RA-ILD patients and 84 (27.5%) IPF patients developed AE. The median survival time (MST) after AE of RA-ILD and IPF was 277 days and 60 days, respectively (log rank, p = 0.038). In a multivariate analysis, hypoalbuminemia [odds ratio (O.R.) 0.090 (95%CI 0.011-0.733), p = 0.012] and % carbon monoxide diffusion capacity (%DLCO) [O.R. 0.810 (95%CI 0.814-0.964), p < 0.01] were independent risk factors for AE. AE was the most frequent cause of death of RA-ILD and IPF. CONCLUSION: RA-ILD patients could develop AE, and AE was not uncommon in RA-ILD or IPF. %DLCO and hypoalbuminemia were predictive factors of AE in RA-ILD. The prognosis after AE of RA-ILD was significantly better than that of IPF. The most frequent cause of death in RA-ILD and IPF was AE.

A case report, a case who developed limited cutaneous scleroderma and pulmonary hypertension 8 years after diagnosis of anti-centromere antibody-positive Sjögren syndrome.

A 52-year-old woman was diagnosed as having anti-centromere antibody (ACA)-positive primary Sjögren syndrome (pSS). Eight years later, she visited our hospital because she had developed dyspnoea. She was diagnosed as having pulmonary arterial hypertension (PAH) with pulmonary veno-occlusive disease on the basis of the results of right heart catheterisation, a severe decrease in diffusing capacity of the lung for carbon monoxide (DLCO, 17%) and desaturation (69%) after a 6-minute walk test. She was also diagnosed as having limited cutaneous systemic sclerosis (lcSSc) because she had developed finger sclerosis. The six-minute walk distance had improved by 54 m 3 months after commencing treatment with tadalafil. Clinicians should be alert to the possibility of patients with ACA-positive SS developing lcSSc and PAH during their clinical course.

[LONG-TERM RESULTS OF AIRBORNE POLLEN SURVEYS IN THE JAPANESE ARCHIPELAGO FROM THE PERSPECTIVE OF POLLEN ANTIGEN].

BACKGROUND: In 1986, the Ministry of Health and Welfare started an airborne pollen survey as part of measures against JC pollinosis. We reported the important tree pollen antigens in 2016. We have now estimated the longitudinal investigated results for successful prevention and treatment for allergic symptoms related to grass and weed pollen in Japan. METHOD: Since July 1986 we have monitored airborne pollen, year- round, using a gravitational pollen sampler (Durham's sampler), at more than 20 locations across Japan. Specimens were mailed to our facility, where they were stained with Calberla solution, counted under an optical microscope, and converted to the number of pollen per square centimeter. For convenience the number of collected pollen were compiled every six months, with the January to June samples classified as spring pollen and the July to December as autumn pollen even same family. RESULT: Total pollen counts at each location were extremely small compared to tree-pollen, averaging 73~650 pollen grains per year. The Sagamihara location had the greatest count. Unlike cedar and cypress there were no significant annual fluctuations, but grass and Ambrosia pollen counts are increasing in some regions. Spring grass pollen gave the largest count, at 30% of the total collected. CONCLUSION: This indicated we need to examine the rinoconjuctivitis and oral allergy syndrome related to herbaceous pollen carefully.The importance of airborne pollen surveys for the treatment of the patients with pollen allergies was suggested.

Lung Sound Analysis and the Respiratory Cycle Dependence of Impulse Oscillometry in Asthma Patients.

Objective A lung sound analysis (LSA) is useful for detecting airway inflammation and obstruction in patients with asthma. To elucidate the mechanism of LSA, we investigated the relationship between the exhalation-to-inhalation sound pressure ratio in the low frequency range between 100 and 195 Hz (E/I LF) and the respiratory cycle dependence of impulse oscillometry (IOS) parameters. Methods Asthma patients underwent IOS [resistance of the respiratory system at 5 Hz (R5) and 20 Hz (R20), the reactance area (AX), resonant frequency of reactance (Fres), and reactance of the respiratory system at 5 Hz (X5) ], spirography, and an LSA. The correlation between the LSA-derived E/I LF values and the respiratory cycle dependence of the IOS parameters was analyzed. Patients Thirty-four patients with mild to moderate bronchial asthma, who had not received oral or inhaled corticosteroids and who had no episodes of rumbling or wheezing were examined. Results The E/I LF value was significantly correlated with the differences of the R5 and R5-R20 values between exhalation and inhalation (p=0.035 and p=0.050) in a multivariate analysis. Conclusion E/I LF appears to be an index that expresses the respiratory cycle dependence of asthma as well as IOS.

Disseminated Cryptococcosis with Marked Eosinophilia in a Postpartum Woman.

Disseminated cryptococcosis usually develops in immunosuppressed patients. A 33-year-old postpartum woman developed disseminated cryptococcosis with marked eosinophilia. She presented with a cough and a week-long fever. A computed tomography scan showed multiple pulmonary nodules randomly distributed. Eosinophils were observed to have increased in number in both her peripheral blood and bronchoalveolar lavage fluid. A transbronchial lung biopsy and cerebrospinal fluid specimens revealed findings consistent with cryptococcal infection. Disseminated cryptococcosis can present with marked eosinophilia of the peripheral blood and lung tissues. Additionally, the postpartum immune status may sometimes be involved in the development of opportunistic infections in previously healthy women.

Lung sound analysis helps localize airway inflammation in patients with bronchial asthma.

PURPOSE: Airway inflammation can be detected by lung sound analysis (LSA) at a single point in the posterior lower lung field. We performed LSA at 7 points to examine whether the technique could identify the location of airway inflammation in patients with asthma. PATIENTS AND METHODS: Breath sounds were recorded at 7 points on the body surface of 22 asthmatic subjects. Inspiration sound pressure level (ISPL), expiration sound pressure level (ESPL), and the expiration-to-inspiration sound pressure ratio (E/I) were calculated in 6 frequency bands. The data were analyzed for potential correlation with spirometry, airway hyperresponsiveness (PC20), and fractional exhaled nitric oxide (FeNO). RESULTS: The E/I data in the frequency range of 100-400 Hz (E/I low frequency [LF], E/I mid frequency [MF]) were better correlated with the spirometry, PC20, and FeNO values than were the ISPL or ESPL data. The left anterior chest and left posterior lower recording positions were associated with the best correlations (forced expiratory volume in 1 second/forced vital capacity: r=-0.55 and r=-0.58; logPC20: r=-0.46 and r=-0.45; and FeNO: r=0.42 and r=0.46, respectively). The majority of asthmatic subjects with FeNO ≥70 ppb exhibited high E/I MF levels in all lung fields (excluding the trachea) and V50%pred <80%, suggesting inflammation throughout the airway. Asthmatic subjects with FeNO <70 ppb showed high or low E/I MF levels depending on the recording position, indicating uneven airway inflammation. CONCLUSION: E/I LF and E/I MF are more useful LSA parameters for evaluating airway inflammation in bronchial asthma; 7-point lung sound recordings could be used to identify sites of local airway inflammation.

A 63-Year-Old Woman With Progressive Dyspnea After Remission of Lymphoma.

CASE PRESENTAION: A 63-year-old woman visited our hospital for a further evaluation of progressive dyspnea. She had developed a progressive airflow obstruction after 3 years' remission of non-Hodgkin's lymphoma (follicular mixed cell type), which had been treated with chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). The patient's primary care physician had diagnosed her as having COPD and bronchial asthma and had treated her with medications including inhaled corticosteroids, tiotropium, and oral erythromycin. Her dyspnea had gradually worsened, however, and she had a score of 4 on the modified Medical Research Council dyspnea scale at the time of admission to our hospital.

Airway inflammation phenotype prediction in asthma patients using lung sound analysis with fractional exhaled nitric oxide.

BACKGROUND: We previously reported the results of lung sound analysis in patients with bronchial asthma and demonstrated that the exhalation-to-inhalation sound pressure ratio in the low frequency range between 100 and 200 Hz (E/I LF) was correlated with the presence of airway inflammation and airway obstruction. We classified asthma patients by airway inflammation phenotype using the induced sputum eosinophil and neutrophil ratio and determined whether this phenotype could be predicted using E/I LF and fractional exhaled nitric oxide values. METHODS: Steroid-naive bronchial asthma patients were classified into four phenotypes, including "Low inflammation" (35 patients), "Eosinophilic type" (58 patients), "Neutrophilic type" (15 patients), and "Mixed type" (15 patients) based on the results of induced sputum examinations. The E/I LF data and FeNO levels were then evaluated for the four phenotype groups; the prediction powers of these two indices were then analyzed for each phenotype. RESULTS: The median E/I LF value was highest in the "Mixed type" and lowest in the "Low inflammation" group. FeNO differentiated between the "Low inflammation" and "Eosinophilic type" groups, "Low inflammation" and "Neutrophilic type" groups, and "Neutrophilic type" and "Mixed type" (p < 0.0001, p = 0.007, and p = 0.04, respectively). E/I LF differentiated between the "Low inflammation" and "Eosinophilic type" groups (p = 0.006). E/I LF could distinguish the "Mixed type" group from the "Low inflammation" and "Eosinophilic type" groups (p = 0.002). CONCLUSIONS: A combination of the E/I LF value and FeNO may be useful for the classification of the airway inflammation phenotype in patients with bronchial asthma.

LONGITUDINAL MONITORING OF TREE AIRBORNE POLLEN IN JAPAN.

RATIONAL: In Japan patients with Japanese Cedar (JC) pollinosis have increased nation widely since the latter of 1970's. The Ministry of Health and Welfare of Japanese Governments has begun to take preventive measures against JC pollinosis and airborne pollen monitoring has begun to investigate as a causative agent since 1986. We have estimated the longitudinal investigation result for successful prevention and treatment against pollinosis in Japan. METHOD: We have monitored airborne pollen all year around since July 1986 by gravitational pollen sampler, Durham's sampler, at more than 20 locations in the Japanese Islands. Pollen samples were sent to our hospital and counted pollen number per cm2 after stained by Calberla solution and then classified main pollen grains as a causative agent of pollinosis. RESULT AND DISCUSSION: JC pollen number was the most of all, more than 40%, next cypress family, about 20%. They were occupied of more than 60% of all and they increased with the remarkable annual fluctuation as the allergen of JC pollinosis. Beech family pollen counting were also increasing and occupied about 10% of all pollen counts. In Hokkaido the prevalence of birch family pollen count was larger than that in other districts. There is cross-reactivity between beech and birch family which related with oral allergic syndrome.Perspective and Conclusion: In future new occurrences of oral allergy syndrome due to increasing allergic tree pollen grains would be appeared. The contentious pollen research should be important for patients with pollinosis in Japan.

Lung sound analysis can be an index of the control of bronchial asthma.

BACKGROUND: We assessed whether lung sound analysis (LSA) is a valid measure of airway obstruction and inflammation in patients with bronchial asthma during treatment with inhaled corticosteroids (ICSs). METHODS: 63 good adherence patients with bronchial asthma and 18 poor adherence patients were examined by LSA, spirometry, fractional exhaled nitric oxide (FeNO), and induced sputum. The expiration-to-inspiration lung sound power ratio at low frequencies between 100 and 200 Hz (E/I LF) obtained by LSA was compared between healthy volunteers and bronchial asthma patients. Next, post-ICS treatment changes were compared in bronchial asthma patients between the good adherence patients and the poor adherence patients. RESULTS: E/I LF was significantly higher in bronchial asthma patients (0.62 ± 0.21) than in healthy volunteers (0.44 ± 0.12, p < 0.001). The good adherence patients demonstrated a significant reduction in E/I LF from pre-treatment to post-treatment (0.55 ± 0.21 to 0.46 ± 0.16, p = 0.002), whereas the poor adherence patients did not show a significant change. The decrease of E/I LF correlated with the improvement of FEV1/FVC ratio during the ICS treatment (r = -0.26, p = 0.04). The subjects with higher pre-treatment E/I LF values had significantly lower FEV1/FVC and V50,%pred (p < 0.001), and significantly higher FeNO and sputum eosinophil percentages (p = 0.008 and p < 0.001, respectively). CONCLUSIONS: The E/I LF measurement obtained by LSA is useful as an indicator of changes in airway obstruction and inflammation and can be used for monitoring the therapeutic course of bronchial asthma patients.

Effects of tiotropium on lung function in current smokers and never smokers with bronchial asthma.

The effects of tiotropium, an inhaled long-acting muscarinic antagonist, on lung function were investigated in current smokers and nonsmokers with asthma treated with inhaled corticosteroids (ICSs) and other asthma controllers: inhaled long-acting ß2 agonists, leukotriene receptor antagonists, and/or theophylline. We conducted a double-blind, placebo-controlled study of an inhaled single dose of tiotropium in 9 asthmatics currently smoking and 9 asthmatics who have never smoked in a crossover manner. Lung function was measured before and 1, 3, and 24 h after inhalation of 18 µg of tiotropium or a placebo. The primary outcome was a change in forced expiratory volume in 1 s (FEV1) from the baseline, and the secondary outcomes were changes in peak expiratory flow rate (PEFR), V˙50, and V˙25. At baseline, asthmatics with and without a smoking history had a mean FEV1 of 2590 ml and 2220 ml and were taking a mean dose of ICSs of 1208 and 1000 µg/day, respectively. The increase from the baseline FEV1 was 169 ml and 105 ml higher at 3 h after tiotropium than after the placebo in current smokers and nonsmokers, respectively. PEFR, V˙50, and V˙25 were also significantly increased after tiotropium as compared with the placebo in both study groups. Changes in FEV1 and PEFR tended to be greater in asthmatics currently smoking than in subjects who have never smoked, although there were no statistical differences at any time points. Tiotropium resulted in improved lung function and symptoms both in current smoker and nonsmoker asthmatics. These findings suggest that tiotropium will provide a new strategy for the treatment of bronchial asthma.

Peripheral bronchial obstruction evaluation in patients with asthma by lung sound analysis and impulse oscillometry.

BACKGROUND: Computer-aided lung sound analysis (LSA) has been reported to be useful for evaluating airway inflammation and obstruction in asthma patients. We investigated the relation between LSA and impulse oscillometry with the evaluation of peripheral airway obstruction. METHODS: A total of 49 inhaled corticosteroid-naive bronchial asthma patients underwent LSA, spirometry, impulse oscillometry, and airway hyperresponsiveness testing. The data were analyzed to assess correlations between the expiration: inspiration lung sound power ratio (dB) at low frequencies between 100 and 195 Hz (E/I LF) and various parameters. RESULTS: E/I LF and X5 were identified as independent factors that affect V˙50,%predicted. E/I LF showed a positive correlation with R5 (r = 0.34, p = 0.017), R20 (r = 0.34, p = 0.018), reactance area (AX, r = 0.40, p = 0.005), and resonant frequency of reactance (Fres, r = 0.32, p = 0.024). A negative correlation was found between E/I LF and X5 (r = -0.47, p = 0.0006). E/I LF showed a negative correlation with FEV1/FVC(%), FEV1,%predicted, V˙50,%predicted, and V˙25,%predicted (r = -0.41, p = 0.003; r = -0.44, p = 0.002; r = -0.49, p = 0.0004; and r = -0.30, p = 0.024, respectively). E/I LF was negatively correlated with log PC20 (r = -0.30, p = 0.024). Log PC20, X5, and past smoking were identified as independent factors that affected E/I LF level. CONCLUSIONS: E/I LF as with X5 can be an indicator of central and peripheral airway obstruction in bronchial asthma patients.

Assessment of anti-inflammatory effect from addition of a long-acting beta-2 agonist to inhaled corticosteroid.

BACKGROUND: Inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA) are thought to enhance the pharmacologic action of one another by a synergistic effect. OBJECTIVE: We compared a group of patients who used ICS monotherapy with a group treated with ICS/LABA combination and evaluated the LABAs with regard to the synergistic effect on the anti-inflammatory action of the ICS. METHODS: This study was conducted with 107 adult patients with mild-to-moderate bronchial asthma. The patients were randomly assigned to either ICS monotherapy (n = 55) or an ICS/LABA combination (n = 52). Both groups were assessed for respiratory function, fractional exhaled nitric oxide, induced sputum, and airway hyperresponsiveness before and after 6 months of treatment. RESULTS: The ICS/LABA combination group showed significantly greater improvement than the ICS monotherapy group in the forced expiratory volume in 1 second/forced vital capacity (p < 0.01), forced expiratory volume in 1 second % predicted (p < 0.05), % predicted maximal expiratory flow at 50% (p < 0.01), % predicted maximal expiratory flow at 25% (p < 0.05), and airway hyperresponsiveness (p < 0.01). However, the two groups did not show significant differences in changes in the fractional exhaled nitric oxide (p = 0.47) or the percentage of eosinophils in the central (p = 0.85) or peripheral sputum (p = 0.98). CONCLUSION: The significant improvement in respiratory function in the ICS/LABA combination treatment group compared with the ICS monotherapy group indicated an additive bronchodilator effect of the LABA. However, the two groups did not differ in airway inflammation, which indicated that a synergistic effect of the LABA on enhancing the anti-inflammatory action of the ICS was not clinically apparent.

Influence of cigarette smoking on airway inflammation and inhaled corticosteroid treatment in patients with asthma.

BACKGROUND: Cigarette smoking induces neutrophilic airway inflammation and relative resistance to inhaled corticosteroids (ICS). OBJECTIVE: We evaluated the influence of cigarette smoking on airway inflammation in patients with asthma and also compared the effect of ICS between smoking and nonsmoking in patients with asthma. METHODS: Smokers with asthma (n = 81) and nonsmokers with asthma (n = 52) were recruited for the study. We examined lung function, fractional exhaled nitric oxide (FeNO) concentration, induced sputum, and acetylcholine inhalation before and 6 months after inhaling budesonide at 800 µg/day. Thirty-four healthy volunteers were included as controls. RESULTS: Smokers with asthma showed a lower forced expiratory volume in 1 second (FEV1) to forced volume capacity (FVC) ratio (p < 0.05), a lower FeNO (p < 0.01), a lower eosinophil proportion (p < 0.05), and a higher neutrophil proportion (p < 0.05) in induced sputum than nonsmokers with asthma. Bronchial hyperresponsiveness (the provocative concentration of acetylcholine [Ach] that produced a 20% fall in FEV1 [PC20-Ach]) was increased in smokers with asthma compared with nonsmokers with asthma (p < 0.05). Both smokers with asthma and nonsmokers with asthma exhibited more prominent airway obstruction, a higher FeNO, and a higher percentage of sputum eosinophils than the controls (p < 0.05 to p < 0.001, each). After 6 months of treatment with inhaled budesonide at 800 µg/day, the improvement in lung function (FEV1 to FVC ratio, flow at 50% forced vital capacity [V50% predicted] and flow at 25% forced vital capacity [V25% predicted]), the eosinophil proportion in induced sputum and PC20-Ach were lower in smokers with asthma than nonsmokers with asthma (p < 0.05). CONCLUSION: Smokers with asthma showed neutrophilic airway inflammation in addition to eosinophilic inflammation, and cigarette smoking impaired the efficacy of ICS treatment in mild-to-moderate asthma. These findings have important implications for the management of patients with asthma and who smoke.

Trigger of bronchial hyperresponsiveness development may not always need eosinophilic airway inflammation in very early stage of asthma.

BACKGROUND: Cough variant asthma (CVA), a suggested precursor of standard bronchial asthma (SBA), is characterized by positive bronchial hyperresponsiveness (BHR) and a chronic cough response to bronchodilator that persists for >8 weeks. OBJECTIVE: Airway inflammation, BHR, and airway obstructive damage were analyzed to assess whether CVA represents early or mild-stage SBA. METHODS: Patients with newly diagnosed CVA (n = 72) and SBA (n = 84) naive to oral or inhaled corticosteroids and without exacerbated asthma were subjected to spirometry, impulse oscillometry, BHR tests, sputum induction, and fractional exhaled nitric oxide measurements. RESULTS: In the patients with CVA, spirometry demonstrated higher forced expiratory volume in 1 second (FEV1) to forced vital capacity ratio, FEV1 percent predicted, flow volume at 50% of vital capacity % predicted, and flow volume at 25% of vital capacity % predicted values, and impulse oscillometry demonstrated lower R5-Z20, AX, and Fres, and higher X5 values. In addition, the fractional exhaled nitric oxide and sputum eosinophil numbers were lower and the PC20 was higher than in patients with moderate SBA. However, these factors were similar in the patients with CVA and in the patients with intermittent mild SBA. A significantly smaller proportion of the patients with CVA had increased sputum eosinophils than the patients with intermittent mild SBA (p < 0.0001). However, interestingly, among the patients with CVA, no significant differences in the PC20 values were found between the patients with and those without increased sputum eosinophils. CONCLUSIONS: All measures of central and peripheral airway obstruction, eosinophilic inflammation, and airway hyperresponsiveness in patients with CVA were milder than in patients with moderate SBA but were similar to those of patients with intermittent mild SBA. In CVA, the BHR was not affected by airway eosinophilic inflammation, which indicated that the very early development of BHR may not always need airway eosinophilic inflammation.