Questionnaire for diagnosing asthma-COPD overlap in COPD: Development of ACO screening questionnaire (ACO-Q).

BACKGROUND: The considerable prevalence and worse outcomes of asthma-COPD overlap (ACO) in COPD have been reported, and optimal introduction of ICS is essential for ACO. However, diagnostic criteria for ACO consist of multiple laboratory tests, which is challenging during this COVID-19 era. The purpose of this study was to create a simple questionnaire to diagnose ACO in patients with COPD. METHODS: Among 100 COPD patients, 53 were diagnosed with ACO based on the Japanese Respiratory Society Guidelines for ACO. Firstly, 10 candidate questionnaire items were generated and further selected by a logistic regression model. An integer-based scoring system was generated based on the scaled estimates of items. RESULTS: Five items, namely a history of asthma, wheezing, dyspnea at rest, nocturnal awakening, and weather- or season-dependent symptoms, contributed significantly to the diagnosis of ACO in COPD. History of asthma was related to FeNO >35 ppb. Two points were assigned to history of asthma and 1 point to other items in the ACO screening questionnaire (ACO-Q), and the area under the receiver operating characteristic curve was 0.883 (95% CI: 0.806-0.933). The best cutoff point was 1 point, and the positive predictive value was 100% at a cutoff of 3 points or higher. The result was reproducible in the validation cohort of 53 patients with COPD. CONCLUSIONS: A simple questionnaire, ACO-Q, was developed. Patients with scores ≥3 could be reasonably recommended to be treated as ACO, and additional laboratory testing would be recommended for patients with 1 and 2 points.

[THE OVERLAPPING ELIGIBILITY FOR BIOLOGICS IN PATIENTS WITH SEVERE ASTHMA AND PHENOTYPES].

BACKGROUND: Biologics are an important treatment option for patients with severe asthma. Four biologics are available in Japan, and an overlapping eligibility has been observed. The eligibility and availability of drugs depend on the local regulations of different countries. However, there is no precise information about the eligibility for biologics, including dupilumab, in Japan. The aim of the study was to investigate the overlapping eligibility and to analyze the phenotypes of patients with multiple eligibility. METHODS: In this observational study, a retrospective chart review of patients was performed. The eligibility criteria for omalizumab were IgE 30-1500IU/mL and positive IgE for perennial aeroallergen. The eligibility criteria for IL-5-targeted biologics (mepolizumab and benralizumab) were eosinophil counts (Eos) > 150µL, while those for dupilumab were Eos > 150µL or fraction of exhaled nitric oxide (FeNO) > 150ppb or IgE > 167IU/mL. Severe asthma was defined by the severity criteria under treatment based on Japanese guidelines for adult asthma. RESULTS: One hundred patients with severe asthma were identified. The eligibility for omalizumab, IL-5-targeted therapies, and dupilumab was 43%, 69%, and 82%, respectively. Thirty percent of the patients were eligible for all the four biologics and showed the lowest FEV1, frequent exacerbation history, and the highest levels of Eos, FeNO, and serum periostin. Only 11% of the patients were not indicated for any biologics. CONCLUSION: A considerable portion of patients was eligible for all the biologics. Asthma control was poor, and type 2 inflammation was prominent in such patients.

Comprehensive analysis of allergen-specific IgE in COPD: mite-specific IgE specifically related to the diagnosis of asthma-COPD overlap.

BACKGROUND: Although the relationship between allergic sensitization and increased respiratory symptoms of chronic obstructive pulmonary disease (COPD) has been suggested, which allergen has a significant effect on COPD pathology is unclear. This study aimed to identify the specific IgE related to clinical features of COPD and the diagnosis of asthma-COPD overlap (ACO). METHODS: We recruited 76 patients with COPD and analyzed 39 IgE using panel IgE test (View Allergy 39®). ACO was diagnosed according to the Japanese Respiratory Society Guidelines. RESULTS: As for perennial aeroallergens, the positivity for moth (31.5%), Candida (23.7%), Dermatophagoides pteronyssinus (22.4%) and house dust (22.4%), and concerning pollen, Japanese cedar (35.5%) and Japanese cypress (22.2%) exceeded 20%. Only the positivity of IgE for Dermatophagoides pteronyssinus and house dust was significantly higher in ACO compared with that in non-ACO COPD. Moreover, it contributed to the diagnosis of ACO in an IgE class-dependent manner. Patients with cockroach IgE exhibited higher residual volume, whereas those with Japanese cedar IgE exhibited better diffusion capacity than negative patients. The contribution for ACO diagnosis by the receiver operating characteristic curve analysis was comparable among total IgE (cutoff value: 158 IU/mL), blood eosinophil count (234/µL), and fraction of exhaled nitric oxide (31.0 ppb). CONCLUSIONS: The prominent role of mite-specific IgE in the diagnosis and pathology of ACO and the potentially detrimental effect of cockroach sensitization on air trapping in COPD were suggested. The finding highlights the future development of a treatment targeting IgE as a treatable trait in COPD.

[PREVALENCE OF FUNCTIONAL DYSPEPSIA SYMPTOMS IN PATIENTS WITH ASTHMA].

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common comorbidity among patients with asthma. In addition, functional dyspepsia (FD) is characterized by upper abdominal symptoms without organic disease manifestations. However, the prevalence of FD among patients with asthma remains uninvestigated; therefore, herein, we investigated the prevalence of dyspepsia symptoms in these patients. METHODS: We recruited 156 patients with asthma from the outpatient clinic of Teikyo University Hospital and investigated the prevalence of dyspepsia symptoms using the modified Frequency Scale for the Symptoms of GERD. Further, the relationship between dyspepsia symptoms and clinical background of asthma was also investigated. RESULTS: Certain digestive organ symptoms were exhibited by 83% of patients with asthma, dyspepsia symptoms by 44%, and reflux symptoms by 26%. The dyspepsia-dominant group showed significantly higher female ratio and numerically lower %FEV1 than the asymptomatic group. In the group with dyspepsia score >5 points, the ratio of patients undergoing step 4 asthma treatment and the ratio of those using long-acting muscarinic receptor antagonist were higher than those in the group with a score <5 points. Furthermore, endoscopic diagnosis was also made in 84 patients and the prevalence of FD was 21%. CONCLUSION: A considerable proportion of patients with asthma exhibited dyspepsia symptoms, and the asthma severity in patients with dyspepsia was higher than those in asymptomatic patients. Based on the current findings, more attention should be directed to FD, in addition to GERD, as a comorbidity of the digestive system in patients with asthma.