Allergic bronchopulmonary aspergillosis with atopic, nonatopic, and sans asthma-Factor analysis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) develops in the presence or absence of asthma, either atopic or nonatopic. We have tried to explore the essential components in the pathogenesis of the disease, which are either consistent and variable according to the presence and type of asthma. METHODS: Non-cystic fibrosis ABPA cases satisfying Asano's criteria were extracted from a prospective registry of ABPA and related diseases in Japan between 2013 and 2023. According to the type of preceding asthma, ABPA was classified into three groups: ABPA sans asthma (no preceding asthma), ABPA with atopic asthma, and ABPA with nonatopic asthma. Exploratory and confirmatory factor analyses were performed to identify the components that determined the clinical characteristics of ABPA. RESULTS: Among 106 cases of ABPA, 25 patients (24%) had ABPA sans asthma, whereas 57 (54%) and 24 (23%) had ABPA with atopic and nonatopic asthma, respectively. Factor analysis identified three components: allergic, eosinophilic, and fungal. Patients with atopic asthma showed the highest scores for the allergic component (p < .001), defined by total and allergen-specific IgE titers and lung opacities, and the lowest scores for the fungal component defined by the presence of specific precipitin/IgG or positive culture for A. fumigatus. Eosinophilic components, including peripheral blood eosinophil counts and presence of mucus plugs/high attenuation mucus in the bronchi, were consistent among the three groups. CONCLUSION: The eosinophilic component of ABPA is considered as the cardinal feature of ABPA regardless of the presence of preceding asthma or atopic predisposition.

New clinical diagnostic criteria for allergic bronchopulmonary aspergillosis/mycosis and its validation.

BACKGROUND: There are several clinical diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA). However, these criteria have not been validated in detail, and no criteria for allergic bronchopulmonary mycosis (ABPM) are currently available. OBJECTIVE: This study proposes new diagnostic criteria for ABPA/ABPM, consisting of 10 components, and compares its sensitivity and specificity to existing methods. METHODS: Rosenberg-Patterson criteria proposed in 1977, the International Society for Human and Animal Mycology (ISHAM) criteria proposed in 2013, and this new criteria were applied to 79 cases with pathological ABPM and the control population with allergic mucin in the absence of fungal hyphae (n = 37), chronic eosinophilic pneumonia (n = 64), Aspergillus-sensitized severe asthma (n = 26), or chronic pulmonary aspergillosis (n = 24). These criteria were also applied to the 179 cases with physician-diagnosed ABPA/ABPM in a nationwide Japanese survey. RESULTS: The sensitivity for pathological ABPM with Rosenberg-Patterson criteria, ISHAM criteria, and this new criteria were 25.3%, 77.2%, and 96.2%, respectively. The sensitivity for physician-diagnosed ABPA/ABPM were 49.2%, 82.7%, and 94.4%, respectively. The areas under the curve for the receiver-operating characteristic curves were 0.85, 0.90, and 0.98, respectively. The sensitivity for ABPM cases that were culture-positive for non-Aspergillus fungi were 13.0%, 47.8%, and 91.3%, respectively. CONCLUSIONS: The new diagnostic criteria, compared with existing criteria, showed better sensitivity and specificity for diagnosing ABPA/ABPM.

Exacerbating factors in elderly patients with Mycobacterium avium complex pulmonary disease.

No previous studies have examined Mycobacterium avium complex pulmonary disease (MAC-PD) in only elderly patients ⩾75 years old. Here, we investigated the exacerbating factors of MAC-PD in elderly patients and clarified cases that can be followed up without MAC medication. From April 2011 to March 2019, 126 advanced aged patients at our institute were newly diagnosed with MAC-PD, and could be observed based on radiological findings for over a year. Their medical records were retrospectively examined for clinical and radiological findings at the time of diagnosis and 1 year later. To identify the predictors of exacerbation, clinical characteristics of 109 treatment-naïve patients were compared between exacerbated and unchanged groups. Additionally, the unchanged group was followed for one more year. In the current study, positive acid-fast bacilli smears from the sputum test, the presence of cavitary lesions and extensive radiological findings, particularly abnormal shadows in ⩾3 lobes, were predictive of exacerbation among treatment-naïve elderly MAC-PD patients. In the unchanged group, <10% showed exacerbation of radiological findings within the subsequent year. In conclusion, if the sputum smear is negative, no cavitary lesions are present, and abnormal shadows are restricted to ⩽2 lobes, elderly patients with MAC-PD may remain untreated for a few years.

Evaluation of Inhaled Procaterol for Potential Assist Use in Patients with Stable Chronic Obstructive Pulmonary Disease.

OBJECTIVES: International guidelines recommend the use of long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease (COPD), but the usefulness of short-acting bronchodilator assist use for stable COPD remains uncertain. The purpose of the present study was to objectively demonstrate the effects of assist use of procaterol, a short-acting ß2-agonist, on the respiratory mechanics of stable COPD patients treated with a long-acting bronchodilator using forced oscillation technique (FOT) and conventional spirometry. We also confirmed the length of time for which procaterol assist could significantly improve the pulmonary function. METHODS: We enrolled 28 outpatients with mild to severe COPD (Global Initiative for Obstructive Lung Disease stages I-III), who had used the same long-acting bronchodilator for longer than 3 months and who were in stable condition. All measures were performed using both FOT and spirometry sequentially from 15 min to 2 h after inhalation. RESULTS: Compared to baseline, inhaled procaterol assist use modestly but significantly improved spirometric and FOT measurements within 2 h after inhalation. These significant effects continued for at least 2 h. -Significant correlations were found between parameters -measured by spirometry and those measured by FOT. CONCLUSIONS: Procaterol assist use modestly but significantly improved pulmonary function determined by spirometry and respiratory mechanics in patients with stable COPD treated with long-acting bronchodilators. Thus, inhaled procaterol has the potential for assist use for COPD.

Allergic bronchopulmonary aspergillosis in Japan: A nationwide survey.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease characterized by a hypersensitivity reaction to Aspergillus species colonizing the airways. The clinical characteristics of ABPA may differ depending on genetic and environmental background. We performed a nationwide survey to determine the clinical characteristics of ABPA in Japan. METHODS: In 2013, a questionnaire on physician-diagnosed ABPA/allergic bronchopulmonary mycosis was sent to 903 medical centers specializing in respiratory or allergic diseases. Cases fulfilling the following criteria were categorized as possible ABPA-central bronchiectasis (ABPA-CB): 1) presence of specific serum immunoglobulin E (IgE) antibodies or a positive skin reaction to Aspergillus, and 2) bronchiectasis or mucoid impaction in the central bronchi. RESULTS: Of 499 physician-diagnosed cases reported by 132 clinical centers, 358 cases met the criteria for possible ABPA-CB. Median age of ABPA-CB onset was 57 (interquartile range, 44-68) years; later-onset disease, developing ≥50 years of age, accounted for 66% of the cases and was associated with female sex, delayed onset of asthma, and lower levels of serum IgE. A third of the patients (120 patients, 34%) exhibited low levels of serum total IgE (<1000 IU/mL). Aspergillus species were isolated from sputum in 126/213 cases (59%), and Schizophyllum commune was identified in 12 (6%) patients. During the course of the treatment, ABPA recurred in 169 (48%) cases. CONCLUSIONS: This nationwide survey identified several unique clinical characteristics of ABPA in Japan, such as late-onset, relatively lower serum IgE levels, and frequent recurrences/flares.

The Pathogenesis of Alcohol-Induced Airflow Limitation in Acetaldehyde Dehydrogenase 2-Deficient Mice.

BACKGROUND: In Japanese patients, alcohol-induced asthma is attributed to elevated plasma concentrations of acetaldehyde following alcohol consumption because of an acetaldehyde dehydrogenase 2 gene (ALDH2) polymorphism. The resulting increase in plasma histamine concentrations seems to trigger the onset of asthma symptoms. However, the specific pathogenic mechanism underlying this response remains unclear. ALDH2-deficient mice were therefore generated to investigate the pathogenesis of alcohol-induced asthma. METHODS: ALDH2-deficient mice were generated using embryonic stem cells that were derived from C57BL/6 mice. The resulting mice were backcrossed into the BALB/c mice background. Exon 1 of ALDH2 was replaced with the Neo cassette. Pure ethanol was orally administered to ALDH2-deficient and wild-type mice, and the plasma concentrations of ethanol, acetaldehyde, and histamine, in addition to enhanced pause (Penh) values, were determined and compared between the 2 groups. RESULTS: We established an ALDH2-deficient mouse line to compare responses between wild-type and ALDH2-deficient mice receiving orally administered ethanol. The results showed that the plasma concentrations of acetaldehyde (p < 0.0001) and histamine (p < 0.005) were significantly higher, and the Penh values (p < 0.01) were significantly greater in the ALDH2-deficient mice, although plasma ethanol levels were not different. CONCLUSIONS: We studied the pathogenesis of alcohol-induced asthma using ALDH2-deficient mice. The results demonstrated that alcohol intake resulted in an increase in acetaldehyde levels, and a subsequent increase in histamine levels, which induced airway constriction. Alcohol consumption is known to be an important factor that exacerbates bronchial asthma, and studies investigating this factor are useful for the treatment of patients with alcohol-induced asthma.

[A CASE OF PULMONARY MYCOBACTERIUM ABSCESSUS INFECTION THAT DEVELOPED DURING IMMUNOSUPPRESSIVE THERAPY FOR MYASTHENIA GRAVIS WITH RECURRENT THYMOMA].

A 58-year-old man developed cough, sputum, and low-grade fever during immunosuppressive treatment with corticosteroids and cyclosporine for myasthenia gravis with recurrent thymoma. Since chest CT revealed diffuse nodular opacities in both lung fields, he was referred to our department. Mycobacterium abscessus was repeatedly cultured from his sputum, and he was diagnosed with pulmonary M. abscessus infection. Although both chest radiological findings and clinical symptoms were mild, he required treatment with immunosuppressive agents and systemic anesthesia for resection of the recurrent thymoma. Based on complications and according to the patient's preference, oral treatment with clarithromycin 600 mg/day, levofloxacin 500 mg/day, and faropenem 600 mg/day was initiated on an outpatient basis. Following these treatments, his chest CT findings and clinical symptoms subsided, and the thymoma was successfully resected. Our experience with the present case suggests a possible treatment strategy for M. abscessus infection in immunocompromised and complicated cases.

Mechanism and management of alcohol-induced asthma.

The purpose of the present review is to explain the mechanism of alcohol-induced asthma in Japanese. An oral ethanol provocation test was performed in Japanese asthmatics to measure pulmonary function, blood ethanol, acetaldehyde and histamine. Acetaldehyde dehydrogenase 2 (ALDH2) genotype was determined by polymerase chain reaction (PCR) and ethanol patch test. Human bronchi and mast cells were stimulated with acetaldehyde in vitro. Approximately half of the asthmatic subjects developed bronchoconstriction with concomitant increases in blood acetaldehyde and histamine, which was associated with genetically reduced ALDH2 activities. In vitro acetaldehyde stimulation induced bronchoconstriction and degranulation of human mast cells. Collectively, as a metabolite of alcohol, the elevation of acetaldehyde following alcohol consumption induces airway mast cells to release histamine, which result in exacerbation of asthma in susceptible population.

[Pneumococcal vaccine and influenza vaccine for prevention of exacerbation in patients with COPD].

Patients with chronic obstructive pulmonary diseases (COPD) are frequently exposed to infectious agents including influenza virus and Streptococcus pneumoniae. These infectious agents cause pneumonia and exacerbation of COPD. Prevention as well as anti-microbial treatments is critical for COPD. International guideline recommends that all COPD patients should be vaccinated against influenza virus. While pneumococcal vaccine is recommended for older and severe cases at present. Recently additive effect of pneumococcal vaccine and influenza vaccine are shown.

Asthma in the elderly.

Since the induction of inhaled corticosteroids as a first line therapy for asthma, severe intrac- table asthma had been decreased. Nonetheless, a proportion of severe asthma still remains including asthma in the elderly. To date, the reasons of severity in elderly asthma are con- sidered due to decline of pulmonary function and low adherence to the therapy, both of which are associated with aging. Airway inflammation is also different between younger and elderly asthma. Neutrophilic inflammation is predominant in the elderly asthma possibly due to imnu- nosenescence and asymptomatic aspiration. Inhaled corticosteroids possess a first line therapy for elderly asthma, while additional treatments for neutrophilic inflammation should be consid- ered including long acting bronchodilator and macrolide antibiotics. Similarly non pharma- cological assessment such as vaccine and smoking cessation are also important for elderly asthma.

Clearance of Aspergillus fumigatus is impaired in the airway in allergic inflammation.

BACKGROUND: Aspergillus fumigatus (Af) sometimes colonizes and persists within the respiratory tree in some patients with asthma. To date, the precise reasons why the clearance of Af is impaired in patients with asthma remain unknown. OBJECTIVE: To characterize the effects of allergic airway inflammation on clearance of Af. METHODS: Control and Dermatophagoides farinae (Df) allergen-sensitized BALB/c mice were intranasally infected with Af. After 2 and 9 days of infection, the pathology, fungal burden, and cytokine profile in lung tissue were compared. In a different set of experiments, the phagocytotic activity of alveolar macrophages and the expression of their pathogen recognition receptors also were determined. RESULTS: The Af conidia and neutrophilic airway inflammation disappeared by day 9 after infection in control mice. In Df-sensitized mice, Af conidia and neutrophilic and eosinophilic airway inflammation persisted at day 9 after infection. Compared with control mice, Df allergen-sensitized mice showed significant increases in interleukin (IL)-5 and decreases in IL-12 and interferon-γ in lung tissues at day 2 after infection. Most importantly, compared with Af-infected non-Df-sensitized mice, IL-17 in lung tissues was significantly decreased in Df allergen-sensitized Af-infected mice at day 2 after infection but was significantly increased at day 9. Alveolar macrophages isolated from Df allergen-sensitized mice exhibited significant decreases in phagocytotic activity and expression of Toll-like receptor-4 and dectin-1 compared with those from control mice. CONCLUSION: In the airway of patients with allergy, T-helper cell type 2-dominant immunity potentially affects the expression of pathogen recognition receptors and attenuates cellular defense against Af. Prolonged IL-17 production also could play an important role.

Cysteinyl leukotriene receptor antagonist regulates allergic airway inflammation in an organ- and cytokine-specific manner.

BACKGROUND: Cysteinyl leukotrienes (cys-LTs) are very important factors in the pathophysiology of bronchial asthma. Cys-LT receptor antagonists (LTRAs) decrease allergic airway inflammation. The aim of the present study was to determine the differential effects of LTRAs and corticosteroids on allergic airway inflammation and allergen-specific cytokine production from lymphoid tissues using a murine model of asthma. MATERIAL AND METHODS: Four groups of female BALB/c mice [control (Cont); Dermatophagoides farinae allergen-sensitized (AS); pranlukast (Prl), an LTRA-treated AS; and dexamethasone (Dex)-treated AS] were examined. Lung pathology and cytokine production by prepared mononuclear cells isolated from mediastinal lymph nodes (MLNs) and spleen were compared among these groups. RESULTS: AS mice exhibited allergic airway inflammation and significant increases in allergen-specific Th1 and Th2 cytokines in MLNs and spleen. Prl-treated mice showed significant attenuation of allergic airway inflammation concomitant with reduction of Th2 cytokines and IFN-g in MLNs but not in spleen. In contrast, Dex significantly decreased Th1 and Th2 cytokines in MLNs and also decreased them (except IL-13 and IL-2) in spleen. CONCLUSIONS: The inflammatory effects of cys-LTs could differ in lymphoid organs. LTRAs potentially regulate allergic airway inflammation in an organ- and cytokine-specific manner, while systemic corticosteroid shows nonspecific effects.

A study on the management of acute respiratory tract infection in adults.

Antimicrobials are commonly used to treat acute respiratory tract infection in adults. Furthermore, their overuse has raised concern. We conducted a field survey study that included 170 medical institutions from January 2008 to June 2010. The purpose of this study was to clarify the relationship between the rate of antimicrobial use and patient outcomes with each indication. The study included 1753 patients diagnosed with acute respiratory tract infection. Antimicrobials were used for treatment of 1420 of these patients, whereas 333 cases were not treated with antimicrobials. After 3 days of treatment, patients administered antimicrobials experienced a higher improvement rate than those who did not receive antimicrobial treatment (92.2% vs. 83.3%, p < 0.0001). However, after 7 days of treatment, the rates of improvement for patients in both groups were similar (95.0% and 93.4%, respectively, p = 0.2391). In addition, according to the criteria for the usage of antimicrobials described in the Japanese Respiratory Society guidelines for the management of respiratory tract infection in adults, the patients were classified into the 3 categories (6 indication factors for antimicrobial use): Grade 1, ≤ 2 factors; Grade 2, 3-4 factors; Grade 3, 5-6 factors). The indication factors considered were the following: 1) temperature; 2) purulent sputum or nasal discharge; 3) tonsillar enlargement and tonsillolith/white puss; 4) middle otitis/sinusitis; 5) inflammatory reaction; and 6) high-risk patients. The results indicate that the improvement observed after 3 days of treatment in Grade 2 and Grade 3 patients was significantly higher with antimicrobial treatment than without antimicrobial treatment. In conclusion, the administration of antimicrobials is not recommended in younger patients with no underlying disease. However, the use of antimicrobials is required in patients with a higher relative risk that corresponds to the presence of ≥ 3 of the 6 indication factors for antimicrobial use.

Clinical characteristics of allergic bronchopulmonary mycosis caused by Schizophyllum commune.

BACKGROUND: Allergic bronchopulmonary mycosis (ABPM) is an allergic disease caused by type I and type III hypersensitivity to environmental fungi. Schizophyllum commune, a basidiomycete fungus, is one of the most common fungi that causes non-Aspergillus ABPM. OBJECTIVE: Herein, we attempted to clarify the clinical characteristics of ABPM caused by S. commune (ABPM-Sc) compared with those of allergic bronchopulmonary aspergillosis (ABPA). METHODS: Patients with ABPM-Sc or ABPA were recruited from a nationwide survey in Japan, a multicenter cohort, and a fungal database at the Medical Mycology Research Center of Chiba University. The definition of culture-positive ABPM-Sc/ABPA is as follows: (1) fulfills five or more of the 10 diagnostic criteria for ABPM proposed by Asano et al., and (2) positive culture of S. commune/Aspergillus spp. in sputum, bronchial lavage fluid, or mucus plugs in the bronchi. RESULTS: Thirty patients with ABPM-Sc and 46 with ABPA were recruited. Patients with ABPM-Sc exhibited less severe asthma and presented with better pulmonary function than those with ABPA (p = 0.008-0.03). Central bronchiectasis was more common in ABPM-Sc than that in ABPA, whereas peripheral lung lesions, including infiltrates/ground-glass opacities or fibrotic/cystic changes, were less frequent in ABPM-Sc. Aspergillus fumigatus-specific immunoglobulin (Ig)E was negative in 10 patients (34%) with ABPM-Sc, who demonstrated a lower prevalence of asthma and levels of total serum IgE than those with ABPM-Sc positive for A. fumigatus-specific IgE or ABPA. CONCLUSIONS: Clinical characteristics of ABPM-Sc, especially those negative for A. fumigatus-specific IgE, differed from those of ABPA.

Differential airway inflammatory responses in asthma exacerbations induced by respiratory syncytial virus and influenza virus a.

BACKGROUND: Although respiratory viral infections cause acute exacerbations of asthma, the inflammatory responses vary depending on the causative virus. The purpose of this study was to compare the inflammatory responses in the airways of acute exacerbations of asthma induced by respiratory syncytial virus (RSV) and influenza A virus. METHODS: Sputum induction was performed in asthmatic patients with acute exacerbations induced by RSV (n = 6), influenza A (n = 7), and non-upper respiratory infection (URI)-related factors (n = 8). Sputum concentrations of cysteinyl leukotrienes (cysLTs), TNF-α and IFN-γ were measured. RESULTS: Sputum cysLTs were significantly higher in RSV-induced exacerbations than in influenza A- and non-URI-induced exacerbations. Sputum TNF-α was significantly higher in influenza A-induced exacerbations than in RSV- and non-URI-induced exacerbations. Sputum IFN-γ was significantly lower in RSV-induced exacerbations than in the others. CONCLUSIONS: RSV and influenza A cause acute exacerbations and have different effects on airway inflammation in asthmatic patients. RSV significantly increased cysLTs, while influenza A significantly increased TNF-α in the airway. The underlying mechanism in virus-induced asthma might depend on the viral species.

Dissociation between sensitizing and colonizing fungi in patients with allergic bronchopulmonary aspergillosis.

BACKGROUND: Because allergic bronchopulmonary aspergillosis (ABPA) does not require the presence of Aspergillus fumigatus for diagnosis, serological and radiological findings without cultures usually confirm this condition. OBJECTIVE: To determine which fungi colonize the airways of patients with definitive ABPA. METHODS: We enrolled 11 patients (ages 57.5 ± 17.1 years; male: female, 4:7) with ABPA diagnosed by serological and radiological criteria. Fungi colonizing the airway were identified from mucous plugs that were naturally expectorated or obtained by fiberoptic bronchoscopy. RESULTS: Aspergillus spp. (n = 8) was the most frequently isolated, followed by Schizophyllum commune (n = 4), Candida albicans (n = 2), Rhizopus oryzae (n = 1), and Penicillium spp. (n = 1). Among the Aspergillus spp., A. niger, A. terreus, and A. sydowii were more frequently isolated (total, n = 6) than A. fumigatus (n = 2). Many patients were sensitized with several fungi in addition to Aspergillus, which were dissociated with airway-colonizing fungi. CONCLUSION: Multiple fungal species can colonize the airway, and dissociation between colonizing and sensitizing species frequently occurs in definitive ABPA. Considering the increased prevalence of azole-resistant Aspergillus spp., administering antifungal drugs that target A. fumigatus without identifying which fungal species colonize the airway might be problematic.

Differential effects of dexamethasone and itraconazole on Aspergillus fumigatus-exacerbated allergic airway inflammation in a murine model of mite-sensitized asthma.

BACKGROUND: Fungal exposure is associated with particularly severe asthma. Nevertheless, the effects of anti-fungal treatments on fungus-exacerbated asthma need to be determined. OBJECTIVES: The present study aimed to compare the effects of itraconazole (ITCZ) and dexamethasone (Dex) on Aspergillus fumigatus (Af)-exacerbated preexisting Dermatophagoides farinae (Df) allergen-sensitized allergic airway inflammation. METHODS: Four groups of BALB/c mice were prepared: control, Df-sensitized plus Af-infected mice (Df-Af), and Df-Af mice treated with Dex (Df-Af-Dex) or with ITCZ (Df-Af-ITCZ). Pulmonary pathology and cytokine profiles in the airway were evaluated. In a different set of experiments, the effects of Dex on alveolar macrophage (AM) phagocytosis of Af conidia were determined in Df-sensitized mice. RESULTS: Af infection significantly increased the level of eosinophils and neutrophils in the airway of Df-sensitized mice. While Dex significantly decreased eosinophils, ITCZ significantly decreased both eosinophils and neutrophils in Df-Af mice. Dex significantly decreased IL-5, whereas ITCZ significantly reduced MIP-2 in the airway. Compared to controls, AM isolated from Df-sensitized mice had significantly reduced phagocytotic activity of Af conidia. However, Dex significantly improved phagocytotic activity of AM in Df-sensitized mice. CONCLUSIONS: The present study showed that Dex and ITCZ differently regulated Af-exacerbated allergic airway inflammation; the former inhibits eosinophilic inflammation and the latter inhibits neutrophilic as well as eosinophilic inflammation by regulating different cytokines. Additionally, Dex enhanced the phagocytotic activity of AM in allergic asthma. Thus, a combination of Dex and ITCZ might be effective for the management of fungus-exacerbated asthma.

Case of uncontrolled asthma with Ceriporia lacerata-related broncholithiasis.

An 81-year-old Japanese male patient was treated for asthma. He complained of persistent cough and wheezing. Chest computed tomography scan revealed atelectasis in the right middle lobe. Fiberoptic bronchoscopy was performed. Results showed a calcified stone with filamentous fungi with septa in the right middle lobe bronchus, which was subsequently removed. Ceriporia lacerata was detected repeatedly on sputum culture. Thus, the filamentous fungi were suspected as C. lacerata. Broncholithiasis possibly caused mucous membrane damage owing to C. lacerata colonization, resulting in allergic airway inflammation. Herein, we report a rare case of C. lacerata-related broncholithiasis associated with asthma exacerbation.

Effects of Dupilumab for Asthma-chronic Obstructive Pulmonary Disease Overlap.

No Abstract.