Longitudinal assessment of interstitial lung abnormalities on CT in patients with COPD using artificial intelligence-based segmentation: a prospective observational study.

BACKGROUND: Interstitial lung abnormalities (ILAs) on CT may affect the clinical outcomes in patients with chronic obstructive pulmonary disease (COPD), but their quantification remains unestablished. This study examined whether artificial intelligence (AI)-based segmentation could be applied to identify ILAs using two COPD cohorts. METHODS: ILAs were diagnosed visually based on the Fleischner Society definition. Using an AI-based method, ground-glass opacities, reticulations, and honeycombing were segmented, and their volumes were summed to obtain the percentage ratio of interstitial lung disease-associated volume to total lung volume (ILDvol%). The optimal ILDvol% threshold for ILA detection was determined in cross-sectional data of the discovery and validation cohorts. The 5-year longitudinal changes in ILDvol% were calculated in discovery cohort patients who underwent baseline and follow-up CT scans. RESULTS: ILAs were found in 32 (14%) and 15 (10%) patients with COPD in the discovery (n = 234) and validation (n = 153) cohorts, respectively. ILDvol% was higher in patients with ILAs than in those without ILA in both cohorts. The optimal ILDvol% threshold in the discovery cohort was 1.203%, and good sensitivity and specificity (93.3% and 76.3%) were confirmed in the validation cohort. 124 patients took follow-up CT scan during 5 ± 1 years. 8 out of 124 patients (7%) developed ILAs. In a multivariable model, an increase in ILDvol% was associated with ILA development after adjusting for age, sex, BMI, and smoking exposure. CONCLUSION: AI-based CT quantification of ILDvol% may be a reproducible method for identifying and monitoring ILAs in patients with COPD.

Detrimental impact of late-onset pneumonia on long-term prognosis in oesophageal cancer survivors.

BACKGROUD: Oesophageal cancer patients are prone to early- and late-onset pneumonia after oesophagectomy. We aimed to investigate the incidence rate and impact on the long-term prognosis of late-onset pneumonia in oesophageal cancer survivors who survived for at least one year after oesophagectomy without cancer recurrence. METHODS: We retrospectively reviewed 233 patients with thoracic oesophageal cancer who underwent oesophagectomy with gastric conduit reconstruction between September 2009 and June 2019 at a tertiary referral hospital in Japan. Pneumonia that occurred ≥1 year after oesophagectomy was defined as late-onset pneumonia. RESULTS: Among the 185 oesophageal cancer survivors, 31 (17%) developed late-onset pneumonia. The cumulative incidence rates of late-onset pneumonia 24, 36, and 60 months after oesophagectomy were 6.4%, 10%, and 21%, respectively, whereas pneumonia recurred at 21%, 31%, and 52% within 6, 12, and 24 months, respectively, after the first pneumonia. Chronic obstructive pulmonary disease, postoperative anastomotic leakage, and loss of skeletal muscle mass were independently associated with late-onset pneumonia, and a combination of these factors further increased the risk. Late-onset pneumonia with hospitalisation had the greatest negative impact on the long-term prognosis as non-cancer deaths (HR, 21; p < 0.001), followed by recurrent late-onset pneumonia (HR, 18; p < 0.001). CONCLUSIONS: Late-onset pneumonia in oesophageal cancer survivors is significantly associated with an increased risk of recurrent infections and non-cancer deaths. Chronic obstructive pulmonary disease and postoperative muscle loss are risk factors for late-onset pneumonia, and more intensive pharmacological and nutritional interventions should be considered to improve long-term prognosis after oesophagectomy.

Eosinophilic mucus diseases.

Eosinophilic inflammation is primarily characterized by type 2 immune responses against parasitic organisms. In the contemporary human being especially in developed countries, eosinophilic inflammation is strongly associated with allergic/sterile inflammation, and constitutes an undesired immune reaction. This situation is in stark contrast to neutrophilic inflammation, which is indispensable for the host defense against bacterial infections. Among eosinophilic inflammatory disorders, massive accumulation of eosinophils within mucus is observed in certain cases, and is often linked to the distinctive clinical finding of mucus with high viscosity. Eosinophilic mucus is found in a variety of diseases, including chronic allergic keratoconjunctivitis, chronic rhinosinusitis encompassing allergic fungal sinusitis, eosinophilic otitis media, eosinophilic sialodochitis, allergic bronchopulmonary aspergillosis/mycosis, eosinophilic plastic bronchitis, and eosinophilic asthma. In these pathological conditions, chronic inflammation and tissue remodeling coupled with irreversible organ damage due to persistent adhesion of toxic substances and luminal obstruction may impose a significant burden on the body. Eosinophils aggregate in the hyperconcentrated mucus together with cell-derived crystals, macromolecules, and polymers, thereby affecting the biophysical properties of the mucus. This review focuses on the clinically significant challenges of mucus and discusses the consequences of activated eosinophils on the mucosal surface that impact mucus and persistent inflammation.

Chronic Pasteurella Multocida Bronchitis Diagnosed 3 Years After Onset of Symptoms.

We report a case of chronic infection with Pasteurella multocida in the lower respiratory tract in a man with a cat. A 77-year-old man presented with recurrent hemoptysis accompanied by bronchiectasis and an opacity in the left lung on chest computed tomography. Although the patient was seropositive for Mycobacterium avium complex, repeated sputum cultures were negative for any specific pathogen. Three years later, he was referred to our hospital for hemoptysis with enhanced opacity in the lower lobe of the left lung. Culture of bronchial lavage fluid obtained via bronchoscopy was positive for P. multocida. The patient was treated with amoxicillin-clavulanic acid for 14 days and was instructed to avoid close contact with his cat. His symptoms and chest imaging findings improved and have not recurred during more than 1 1/2 years of follow up. P. multocida can cause chronic lower respiratory infections.

Bilateral Hilar and Mediastinal Lymphadenopathy as an Initial Manifestation of Amyloidosis.

A 75-year-old male visited our hospital with bilateral hilar lymph node swelling detected on chest radiography during an annual medical checkup. Chest computed tomography revealed swelling of multiple hilar mediastinal lymph nodes. Histopathological and immunohistochemical examinations of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimens from the hilar lymph nodes revealed amyloid deposition. Bilateral hilar and mediastinal lymphadenopathies can be the first manifestations of amyloidosis diagnosed using EBUS-TBNA.

Centrilobular emphysema and airway dysanapsis: factors associated with low respiratory function in younger smokers.

Background: Low respiratory function in young adulthood is one of the important factors in the trajectory leading to the future development of COPD, but its morphological characteristics are not well characterised. Methods: We retrospectively enrolled 172 subjects aged 40-49 years with ≥10 pack-years smoking history who underwent lung cancer screening by computed tomography (CT) and spirometry at two Japanese hospitals. Emphysema was visually assessed according to the Fleischner Society guidelines and classified into two types: centrilobular emphysema (CLE) and paraseptal emphysema (PSE). Airway dysanapsis was assessed with the airway/lung ratio (ALR), which was calculated by the geometric mean of the lumen diameters of the 14 branching segments divided by the cube root of total lung volume on a CT scan. Results: Among the subjects, CLE and PSE were observed in 20.9% and 30.8%, respectively. The mean ALR was 0.04 and did not differ between those with and without each type of emphysema. Multivariable regression analysis models adjusted for age, sex, body mass index and smoking status indicated that CLE and a low ALR were independently associated with lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (estimate -1.64 (95% CI -2.68- -0.60) and 6.73 (95% CI 4.24-9.24), respectively) and FEV1 % pred (estimate -2.81 (95% CI -5.10- -0.52) and 10.9 (95% CI 5.36-16.4), respectively). Conclusions: CLE and airway dysanapsis on CT were independently associated with low respiratory function in younger smokers.

Quantification of airway structures by persistent homology.

We propose two types of novel morphological metrics for quantifying the geometry of tubular structures on computed tomography (CT) images. We apply our metrics to identify irregularities in the airway of patients with chronic obstructive pulmonary disease (COPD) and demonstrate that they provide complementary information to the conventional metrics used to assess COPD, such as the tissue density distribution in lung parenchyma and the wall area ratio of the segmented airway. The three-dimensional shape of the airway and its abstraction as a rooted tree with the root at the trachea carina are automatically extracted from a lung CT volume, and the two metrics are computed based on a mathematical tool called persistent homology; treeH0 quantifies the distribution of branch lengths to assess the complexity of the tree-like structure and radialH0 quantifies the irregularities in the luminal radius along the airway. We show our metrics are associated with clinical outcomes.

Associations of fractional exhaled nitric oxide with airway dimension and mucus plugs on ultra-high-resolution computed tomography in former smokers and nonsmokers with asthma.

BACKGROUND: Associations of fractional exhaled nitric oxide (FeNO) with airway wall remodeling and mucus plugs remain to be explored in smokers and nonsmokers with asthma. Ultra-high-resolution computed tomography (U-HRCT), which allows accurate structural quantification of airways >1 mm in diameter, was used in this study to examine whether higher FeNO was associated with thicker walls of the 3rd to 6th generation airways and mucus plugging in patients with asthma. METHODS: The retrospective analyses included consecutive former smokers and nonsmokers with asthma who underwent U-HRCT in a hospital. The ratio of wall area to summed lumen and wall area was calculated as the wall area percent (WA%). Mucus plugging was visually scored. RESULTS: Ninety-seven patients with asthma (including 59 former smokers) were classified into low (<20 ppb), middle (20-35 ppb), and high (>35 ppb) FeNO groups (n = 24, 26, and 47). In analysis including all patients and subanalysis including nonsmokers or former smokers, WA% in the 6th generation airways was consistently higher in the high FeNO group than in the low FeNO group, whereas WA% in the 3rd to 5th generation airways was not. In multivariable models, WA% in the 6th generation airways and the rate of mucus plugging were higher in the high FeNO group than in the low FeNO group after adjusting for age, sex, body mass index, smoking status, lung volume, and allergic rhinitis presence. CONCLUSIONS: Higher FeNO may reflect the inflammation and remodeling of relatively peripheral airways in asthma in both former smokers and nonsmokers.

High attenuation mucus in bronchi with allergic bronchopulmonary mycosis.

BACKGROUND: High-attenuation mucus (HAM) is a specific manifestation of allergic bronchopulmonary mycosis (ABPM) on chest computed tomography (CT). OBJECTIVES: To compare the diagnostic accuracy of the two definitions of HAM and to clarify the clinical and radiographic characteristics of HAM-positive and HAM-negative ABPM. METHODS: CT images at the diagnosis of ABPM using Asano's criteria were retrospectively analysed. In Study #1, radiographic data obtained using the same CT apparatus in a single institute were analysed to determine the agreement between the two definitions of HAM: a mucus plug that is visually denser than the paraspinal muscles or that with a radiodensity ≥70 Hounsfield units. In Study #2, HAM was diagnosed by comparison with the paraspinal muscles in patients with ABPM reporting to 14 medical institutes in Japan. RESULTS: In Study #1, 93 mucus plugs from 26 patients were analysed. A substantial agreement for HAM diagnosis was observed between the two methods, with a κ coefficient of 0.72. In Study #2, 60 cases of ABPM were analysed; mucus plugs were present in all cases and HAM was diagnosed in 45 (75%) cases. The median A. fumigatus-specific IgE titre was significantly lower in HAM-positive patients than in HAM-negative patients (2.5 vs. 24.3 UA /mL, p = .004). Nodular shadows were observed more frequently in the airways distal to HAM than in those distal to non-HAM mucus plugs (59% vs. 32%, p < .001). CONCLUSION: In conclusion, agreement between the two methods to diagnose HAM was substantial. HAM was associated with some immunological and radiographic characteristics, including lower levels of sensitization to A. fumigatus and the presence of distal airway lesions.

Artificial intelligence-based analysis of the spatial distribution of abnormal computed tomography patterns in SARS-CoV-2 pneumonia: association with disease severity.

BACKGROUND: The substantial heterogeneity of clinical presentations in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia still requires robust chest computed tomography analysis to identify high-risk patients. While extension of ground-glass opacity and consolidation from peripheral to central lung fields on chest computed tomography (CT) might be associated with severely ill conditions, quantification of the central-peripheral distribution of ground glass opacity and consolidation in assessments of SARS-CoV-2 pneumonia remains unestablished. This study aimed to examine whether the central-peripheral distributions of ground glass opacity and consolidation were associated with severe outcomes in patients with SARS-CoV-2 pneumonia independent of the whole-lung extents of these abnormal shadows. METHODS: This multicenter retrospective cohort included hospitalized patients with SARS-CoV-2 pneumonia between January 2020 and August 2021. An artificial intelligence-based image analysis technology was used to segment abnormal shadows, including ground glass opacity and consolidation. The area ratio of ground glass opacity and consolidation to the whole lung (GGO%, CON%) and the ratio of ground glass opacity and consolidation areas in the central lungs to those in the peripheral lungs (GGO(C/P)) and (CON(C/P)) were automatically calculated. Severe outcome was defined as in-hospital death or requirement for endotracheal intubation. RESULTS: Of 512 enrolled patients, the severe outcome was observed in 77 patients. GGO% and CON% were higher in patients with severe outcomes than in those without. Multivariable logistic models showed that GGO(C/P), but not CON(C/P), was associated with the severe outcome independent of age, sex, comorbidities, GGO%, and CON%. CONCLUSION: In addition to GGO% and CON% in the whole lung, the higher the ratio of ground glass opacity in the central regions to that in the peripheral regions was, the more severe the outcomes in patients with SARS-CoV-2 pneumonia were. The proposed method might be useful to reproducibly quantify the extension of ground glass opacity from peripheral to central lungs and to estimate prognosis.

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.

Increased blood eosinophils and airflow obstruction as new-onset asthma predictors in the elderly: The Nagahama study.

BACKGROUND: Asthma in the elderly needs more attention in an aging society. However, it is likely to remain underdiagnosed and undertreated. This study aimed to clarify clinical characteristics of new-onset asthma in the elderly, describing the prevalence, predictive factors, and comorbidities after asthma diagnosis of new-onset asthma in the elderly in the general population. METHODS: This community-based prospective cohort study enrolled 9804 generally healthy participants (30-74 years old) in Nagahama City, and conducted a follow-up assessment after 5 years. Elderly participants were those aged ≥65 years at baseline. Patients with new-onset asthma were defined as participants without asthma at baseline assessment and with asthma at the follow-up assessment. RESULTS: Among the 7948 participants analyzed in this study, 28 (1.4%) elderly and 130 (2.2%) non-elderly had new-onset asthma. Multiple logistic regression analysis revealed low forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and high blood eosinophil counts at baseline as predicting factors for new-onset asthma in the elderly. Additionally, subsequent incidence of new-onset asthma was higher in elderly participants with both predictors (high blood eosinophil counts and low FEV1/FVC at baseline) than those with none or one of the predictors before asthma diagnosis. Lastly, elderly patients with new-onset asthma had more frequent comorbidity of moderate to severe sleep disordered breathing than those non-elderly. CONCLUSIONS: Eosinophilic inflammation and airflow obstruction may predict subsequent new-onset asthma after the age of 65 years. Revealing the characteristics of new-onset asthma in the elderly can aid in the prevention of underdiagnosed asthma.

Evaluation of elevated plasma fatty acids as relevant factors for adult-onset asthma: The Nagahama Study.

BACKGROUND: Obesity and increased body mass index (BMI) are the known risk factors for adult-onset asthma. Serum free fatty acid (FFA) and other blood lipid levels are generally elevated in patients with obesity and may be involved in the onset of asthma. However, it remains largely unknown. This study aimed to elucidate the relationship between plasma fatty acids and new-onset asthma. METHODS: This community-based Nagahama Study in Japan enrolled 9804 residents. We conducted self-reporting questionnaires, lung function tests, and blood tests at baseline and 5 years later as follow-up. At the follow-up, plasma fatty acids were measured using gas chromatography-mass spectrometry. Body composition analysis was also measured at the follow-up. The associations between fatty acids and new-onset asthma were evaluated using a multifaceted approach, including targeted partial least squares discriminant analysis (PLS-DA). RESULTS: In PLS-DA for new-onset asthma, palmitoleic acid was identified as the fatty acid most associated with asthma onset. In the multivariable analysis, higher levels of FFA, palmitoleic acid, or oleic acid were significantly associated with new-onset asthma, independent of other confounding factors. The high body fat percentage itself was not the relevant factor, but showed a positive interaction with plasma palmitoleic acid for new-onset asthma. When stratified by gender, the impacts of higher levels of FFA or palmitoleic acid on new-onset asthma remained significant in females, but not in males. CONCLUSIONS: Elevated levels of plasma fatty acids, particularly palmitoleic acid, may be a relevant factor for new-onset asthma.

Evaluation of Bone Mineral Density in Lung Transplant Recipients by Chest Computed Tomography.

INTRODUCTION: Lung transplantation (LT) recipients are at risk of bone mineral density (BMD) loss. Pre- and post-LT BMD loss has been reported in some cross-sectional studies; however, there are limited studies regarding the serial BMD change in LT recipients. The aim of this study was to investigate the serial BMD changes and the clinical characteristics associated with BMD decline. METHODS: This was a single-center, retrospective observational study. BMD was serially measured in thoracic vertebral bodies (Th4, 7, 10) using computed tomography (CT) before and 3 and 12 months after LT. The frequency of osteoporosis and factors associated with pre-LT osteoporosis and post-LT BMD loss were evaluated. The frequency of post-LT compression fracture and its associated factors were also analyzed. RESULTS: This study included 128 adult LT recipients. LT recipients had decreased BMD (151.8 ± 42.2 mg/mL) before LT compared with age-, sex-, and smoking index-matched controls (176.2 ± 35.7 mg/mL). The diagnosis of COPD was associated with pre-LT osteoporosis. LT recipients experience further BMD decline after transplantation, and the percentage of recipients classified as exhibiting osteoporosis increased from 20% at baseline to 43% at 12 months. Recipients who had been taking no or small doses of glucocorticoids before LT had rapid BMD loss after LT. Early bisphosphonate use (within 3 months) after LT attenuated BMD loss and decreased new-onset compression fracture. CONCLUSION: LT recipients are at high risk for BMD loss and compression fracture after LT. Early bisphosphonate use may decrease BMD loss and compression fracture.

A reference equation for lung volume on computed tomography in Japanese middle-aged and elderly adults.

BACKGROUND: Effective use of lung volume data measured on computed tomography (CT) requires reference values for specific populations. This study examined whether an equation previously generated for multiple ethnic groups in the United States, including Asians predominantly composed of Chinese people, in the Multi-Ethnic Study of Atherosclerosis (MESA) could be used for Japanese people and, if necessary, to optimize this equation. Moreover, the equation was used to characterize patients with chronic obstructive pulmonary disease (COPD) and lung hyperexpansion. METHODS: This study included a lung cancer screening CT cohort of asymptomatic never smokers aged ≥40 years from two institutions (n = 364 and 419) to validate and optimize the MESA equation and a COPD cohort (n = 199) to test its applicability. RESULTS: In all asymptomatic never smokers, the variance explained by the predicted values (R2) based on the original MESA equation was 0.60. The original equation was optimized to minimize the root mean squared error (RMSE) by adjusting the scaling factor but not the age, sex, height, or body mass index terms of the equation. The RMSE changed from 714 ml in the original equation to 637 ml in the optimized equation. In the COPD cohort, lung hyperexpansion, defined based on the 95th percentile of the ratio of measured lung volume to predicted lung volume in never smokers (122 %), was observed in 60 (30 %) patients and was associated with centrilobular emphysema and air trapping on inspiratory/expiratory CT. CONCLUSIONS: The MESA equation was optimized for Japanese middle-aged and elderly adults.

Sputum microbiota and inflammatory subtypes in asthma, COPD, and its overlap.

Background: Airway microbiota in asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) remains unknown. Objective: This study with ACO-enriched population aimed to clarify airway microbiota in ACO and in mixed granulocytic inflammation, often detected in ACO and chronic airway diseases. Methods: This is an observational cross-sectional study. Patients with asthma with airflow limitation, ACO, and COPD were enrolled. Blood tests, pulmonary function, exhaled nitric oxide, and sputum tests were conducted. Sputum microbiota was evaluated using the 16S rRNA gene sequencing technique. Results: A total of 112 patients (13 asthma, 67 ACO, and 32 COPD) were examined. There were no significant differences in α-diversity among the 3 diseases. The relative abundances of phylum Bacteroidetes, class Bacteroidia, and genus Porphyromonas were associated with decreased eosinophilic inflammation, and were significantly lower in ACO than in COPD. In a comparison of sputum inflammatory subtypes, the proportion of Haemophilus was numerically highest in the mixed granulocytic subtype, followed by the neutrophilic subtype. Likewise, the proportion of Haemophilus was the highest in the intermediate-high (2%-8%) sputum eosinophil group and lowest in the severe (≥8%) eosinophil group. Clinically, Haemophilus proportion was associated with sputum symptoms. Finally, the proportion of Streptococcus was associated with higher blood eosinophil counts and most severe airflow limitation. Conclusions: Bacteroidia and Porphyromonas abundances in sputum are associated with the eosinophil-low phenotype, and ACO may be characterized by a decrease in these taxa. A mild elevation in sputum eosinophil does not preclude the presence of Haemophilus, which should be noted in the management of obstructive airway diseases.

Sensitization pattern to environmental allergens in a Japanese population.

Background: We previously described the prevalence of allergen-specific IgE in a general population of Japanese adults. Objective: We sought to elucidate allergen sensitization patterns in this population. Methods: Serum samples had been obtained from 800 blood donors aged 20 to 59 years and living in Tokyo, Japan, in 2005 and stored in the Japanese Red Cross Society. These samples were examined for IgE levels, total and specific for 23 allergens or allergen sources correlated with allergic airway diseases using the ImmunoCAP method. Exploratory and confirmatory factor analyses were performed to uncover the relationship among allergen-specific IgE based on their titers. Hierarchical cluster analysis was executed using Ward's method based on standardized factor scores identified through factor analysis. Results: Exploratory factor analysis revealed 6 categories of allergen-specific IgE: specific to 2 types of animals (insects and Dermatophagoides pteronyssinus/animal dander), 2 types of pollens (group 1 [Japanese cedar and cypress] and group 2 [alder, grass, and weeds]), and 2 types of microorganisms (fungi and commensal microorganisms on the skin). The Japanese population was categorized into 3 clusters: (A) nonatopic type, (B) house dust mite-dominant sensitization type, and (C) panatopic type. The panatopic group could be further classified into 2 subclusters positive and negative for fungal sensitization. Conclusions: This study demonstrated that a Japanese population could be divided into 3 clusters according to the sensitization pattern to 6 types of allergens.

Effect of biologic therapy on the humoral immune response to the BNT162b2 vaccine in patients with asthma.

The effect of inhaled corticosteroids (ICS) and biologics on the humoral immune response following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination in patients with asthma is unknown. We prospectively evaluated the humoral immune response 3 weeks (T1) and 6 months (T2) after the second dose of BNT162b2 in 30 SARS-CoV-2-naïve patients with asthma. We measured anti-spike immunoglobulin G (IgG) titers and serum-neutralizing activity against the ancestral SARS-CoV-2 strain. The anti-spike IgG titer and neutralizing activity did not differ significantly between the biologics and non-biologics groups at T1 (P = 0.708 and P = 0.417, respectively) or T2 (P = 0.299 and P = 0.492, respectively). In the multivariate analysis, age and sex were significantly associated with the magnitude of the humoral immune response; however, the use of biologics and ICS dose were not, suggesting that these would not affect BNT162b2 immunogenicity in patients with asthma. Larger studies are needed to validate these findings.

Association of lower plasma citric acid with prolonged cough: the Nagahama study.

Little is known about the association of prolonged cough, a common and troublesome symptom, with metabolic pathways. We aimed to clarify this association using data from the Nagahama cohort, a prospective study of participants from the general population. Self-report questionnaires on prolonged cough were collected at baseline and 5-year follow-up assessments. Blood tests at follow-up were used for gas chromatography-mass spectrometry-based metabolomics. The association between metabolites and prolonged cough was examined using the partial least squares discriminant analysis and multiple regression analysis. Among the 7432 participants, 632 had newly developed prolonged cough at follow-up, which was defined as "new-onset prolonged cough". Low plasma citric acid was significantly associated with new-onset prolonged cough, even after the adjustment of confounding factors including the presence of asthma, upper airway cough syndrome (UACS), and gastroesophageal reflux disease (GERD). A similar association was observed for isocitric acid, 3-hydroxybutyric acid, and 3-hydroxyisobutyric acid. The analysis of these four metabolites revealed that citric acid had the strongest association with new-onset prolonged cough. This significant association remained even when the analysis was confined to participants with UACS or GERD at baseline or follow-up, and these associations were also observed in participants (n = 976) who had prolonged cough at follow-up regardless of baseline status. In conclusion, low blood citric acid may be associated with prolonged cough.