The Effect of Bronchoconstriction by Methacholine Inhalation in a Murine Model of Asthma.

INTRODUCTION: Bronchoconstriction was recently shown to cause airway remodeling and induce allergic airway inflammation in asthma. However, the mechanisms how mechanical stress via bronchoconstriction could induce airway inflammation and remodeling remain unclear. OBJECTIVE: We investigated the effect of bronchoconstriction induced by methacholine inhalation in a murine model of asthma. METHODS: BALB/c female mice were sensitized and challenged with ovalbumin (OVA), followed by treatment with methacholine by a nebulizer twice a day for 7 days. Twenty-four hours after the last methacholine treatment, the bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The BALF was analyzed for total and differential cell counts and cytokine levels. The lung tissues were analyzed for goblet cell metaplasia, thickness of the smooth muscle, and lung fibrosis. The expression of cytokines in the lung was also examined. RESULTS: OVA sensitization and challenge induced infiltration of total cells, macrophages, and eosinophils in the BALF along with goblet cell metaplasia and increased airway smooth muscle hypertrophy. Seven days after the last OVA challenge, untreated mice achieved reduction in airway inflammation, while methacholine maintained the number of BALF total cells, macrophages, and eosinophils. The percentage of goblet cells and the thickness of airway smooth muscle were also maintained by methacholine. Moreover, the treatment of methacholine induced the expression of transforming growth factor (TGF)-ß in the lung. This result indicates that the production of TGF-ß is involved in induction of airway remodeling caused by bronchoconstriction with methacholine. CONCLUSIONS: Repeated bronchoconstriction caused by methacholine inhalation elicited allergic airway inflammation and airway remodeling.

[A CASE OF ANAPHYLAXIS DUE TO STINGING OF A Brachyponera chinensis].

The case involved a man in his forties. While working at the restaurant that the patient runs, the patient experienced a stab-like pain on the left shoulder and developed systemic pruritic eruptions. He was diagnosed with anaphylaxis upon visiting our emergency department. Conjunctival hyperemia, lip swelling, cold sweats, and nausea presented later. A cap fluorescence enzyme immunoassay using the serum of the patient showed specific immunoglobulin E (IgE) positivity for wasps; therefore, we hypothesized that he had anaphylaxis caused by the insect's sting. Insects of the same species as that by which the patient had been stung were collected and finally identified as the Asian needle ant (Brachyponera chinensis). The freeze-dried insects' bodies were sonicated into powders and stored for following examinations. Next, a basophil activation test was performed using the patient's whole blood treated with the reagent above, which showed positivity. Furthermore, a skin prick test using the same reagent showed a positive result, and the reaction increased in a concentrationdependent manner. Based on these results, the patient was diagnosed with anaphylaxis after a sting by the ant. Based on the results of the allergen component specific IgE test, we speculated that the pathogens in this case was group5 allergen of the Asian needle ant. Anaphylaxis following insect stings by this ant has been reported frequently in South Korea. However, it is quite rare in Japan, although the ant is native to Japan. Clinicians should consider that this allergy can occur indoors, unlike allergies to other types of venom.

Beneficial Effect of Early Intervention with Garenoxacin for Bacterial Infection-Induced Acute Exacerbation of Bronchial Asthma and Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma have similar clinical features and are both exacerbated by airway infection. OBJECTIVE: To determine whether garenoxacin mesylate hydrate (GRNX) added to the standard care for bacterial infection-induced acute exacerbation of asthma or COPD in adults has clinical benefits. METHOD: This single-arm clinical trial was conducted from January 2015 to March 2016. Adults with a history of asthma or COPD for more than 12 months were recruited within 48 h of presentation with fever and acute deterioration of asthma or COPD requiring additional intervention. Participants were administered 400 mg GRNX daily for 7 days without additional systemic corticosteroids or other antibiotics. The primary outcome was efficacy of GRNX based on clinical symptoms and blood test results after 7 days of treatment. Secondary outcomes were: (1) comparison of the blood test results, radiograph findings, and bacterial culture surveillance before and after treatment; (2) effectiveness of GRNX after 3 days of administration; (3) analyzation of patient symptoms based on patient diary; and (4) continued effectiveness of GRNX on 14th day after the treatment (visit 3). RESULTS: The study included 44 febrile patients (34 asthma and 10 COPD). Frequently isolated bacteria included Moraxella catarrhalis (n = 6) and Klebsiella pneumoniae (n = 4). On visit 2, 40 patients responded, and no severe adverse events were observed. All secondary outcomes showed favorable results. CONCLUSION: GRNX effectively treated asthma and COPD patients with acute bacterial infection without severe adverse events. Further research with a larger study population is needed.

Unique clinical phenotypes of patients with obstructive sleep apnea in a Japanese population: a cluster analysis.

STUDY OBJECTIVES: In an attempt to better understand the heterogeneity of individuals with obstructive sleep apnea (OSA), unbiased analytic approaches such as cluster analysis have been used worldwide; however, only a few such studies have been conducted for Asian populations alone, despite the potential racial/ethnic differences. We thus applied this approach to a Japanese population with OSA. METHODS: In this single-center, retrospective, observational study, our nocturnal polysomnography dataset included the findings for 1,020 patients between May 2016 and December 2020. Of these, 712 patients met the study criteria: aged > 20 years, fully completed questionnaire, no missing data on all-night full polysomnography, and confirmed OSA diagnosis with an apnea-hypopnea index (AHI) > 15 events/h. We employed hierarchical cluster analysis using demographic data, self-reported symptoms, and polysomnographic data. RESULTS: We identified 5 distinct clinical clusters within the OSA patient population, which were labeled as "classic OSA" (20--67 years, obese, high AHI, high Epworth Sleepiness Scale [ESS]), "milder classic OSA" (22--77 years, obese, high AHI, low ESS), "nonobese and minimally symptomatic" (20--88 years, moderate AHI, low ESS), "excessive sleepiness without severe OSA" (26--79 years, moderate AHI, high ESS), and "older adult and severe OSA" 55--92 years, (high AHI, low ESS). Of these, the last 3 clusters were characterized as nonobese. Notably, we identified the cluster with excessive sleepiness despite less severe OSA. We did not identify any clusters with predominant upper-airway obstruction symptoms because the symptoms were prevalent and equally distributed in all clusters. CONCLUSIONS: We found some unique clinical phenotypes in nonobese patients with OSA in a Japanese population. CITATION: Ida H, Suga T, Nishimura M, Aoki Y. Unique clinical phenotypes of patients with obstructive sleep apnea in a Japanese population: a cluster analysis. J Clin Sleep Med. 2022;18(3):895-902.

Liver Injury by the Traditional Chinese Medicine Hanshirento, Zenshikunshito, and Ninjin'yoeito in a Patient with Lung Cancer: Probable Causality Assessed by the Updated Roussel Uclaf Causality Assessment Method.

INTRODUCTION: Traditional Chinese medicine (TCM) is a traditional treatment based on herbal medicines and holistic healing. It has resulted in both favorable and unfavorable patient outcomes when used to treat cancer. Cancer patients frequently depend on second opinions and folk remedies. In this case, we report the case of TCM inducing repeated moderate liver injury and delay for chemotherapy. CASE PRESENTATION: A 59-year-old woman was diagnosed with lung cancer and conducted surgery a month ago. She went to a TCM specialty clinic expecting a complete cure for the lung cancer, to improve her physical condition, and to enhance her immunity. She received the TCM formulas hanshirento, zenshikunshito, and ninjin'yoeito. After starting these medicines, she felt severe fatigue but continued them for approximately 2 weeks, After discontinuing the medicine, her fatigue was improved. She was admitted to our hospital for adjuvant chemotherapy. On admission, laboratory tests revealed moderate liver injury (AST: 705 U/L, ALT: 1091 U/L). In view of her medication history, the laboratory tests, and her lifestyle history, we thought that moderate liver injury was caused by TCM, employing the Roussel Uclaf Causality Assessment Method (RUCAM). DISCUSSION: TCM are known to be metabolized by the resident bacteria in the small intestine, but the specific metabolic processes are not well understood. Cancer patients sometimes try TCM from their own research to stay healthy. However, as with our case, TCM rarely induces liver injury, which is not well known to TCM users. Medical staffs need to be vigilant with their drug histories, including TCM, if patients have liver injuries.

Correlation of Arterial CO2 and Respiratory Impedance Values among Subjects with COPD.

Chronic obstructive pulmonary disease (COPD) is a respiratory illness characterized by airflow limitation and chronic respiratory symptoms with a global prevalence estimated to be more than 10% in 2010 and still on the rise. Furthermore, hypercapnic subject COPD leads to an increased risk of mortality, morbidity, and poor QoL (quality of life) than normocapnic subjects. Series of studies showed the usefulness of the forced oscillation technique (FOT) to measure small airway closure. Traditional findings suggested that hypercapnia may not be the main treating targets, but recent findings suggested that blood stream CO2 may lead to a worse outcome. This study aimed to seek the relationship between CO2 and small airway closure by using FOT. Subjects with COPD (n = 124; hypercapnia 22 and normocapnia 102) were analyzed for all pulmonary function values, FOT values, and arterial blood gas analysis. Student's t-test, Spearman rank correlation, and multi linear regression analysis were used to analyze the data. COPD subjects with hypercapnia showed a significant increase in R5, R20, Fres, and ALX values, and a greater decrease in X5 value than normocapnic patients. Also, multiple linear regression analysis showed R5 was associated with hypercapnia. Hypercapnia may account for airway closure among subjects with COPD and this result suggests treating hypercapnia may lead to better outcomes for such a subject group.