Associations between birth weight and lung function in a Japanese adult population: The tohoku medical megabank community-based cohort study.

BACKGROUND: Birth weight, as a measure of intrauterine growth, is commonly used in epidemiological studies and is reported to be associated with adult lung function. However, findings regarding this association in previous studies have been inconsistent. Furthermore, no studies have reported associations stratified by age or smoking status, or adjusted for eosinophil count or other parameters related to type 2 airway inflammation. METHODS: This cross-sectional study included 2632 men and 7237 women aged ≥20 years living in Miyagi Prefecture, Japan. Lung function was assessed based on spirometry. Birth weight data were obtained through a questionnaire survey. Analysis of covariance was used to evaluate the associations between birth weight and lung function, adjusting for potential confounders. Stratified analyses by age and smoking status were also conducted, together with a sub-analysis for low birth-weight participants. RESULTS: Birth weight was positively associated with forced expiratory volume in 1 s (FEV1) for both sexes and with vital capacity in women, after adjusting for height, age, smoking status, and parameters related to type 2 airway inflammation. The stratified analysis for smoking status revealed associations in never-smokers and ex-smokers. When stratified by age, the associations were confirmed in middle-aged participants. The effect of smoking status on the FEV1 of low birth-weight participants was not significant. CONCLUSIONS: Our analysis of a large, Japanese adult population showed that birth weight was independently and positively associated with adult lung function, even after adjustment for age, height, smoking status, and parameters related to type 2 airway inflammation.

A Novel Development of Sarcoidosis Following COVID-19 Vaccination and a Literature Review.

BNT162b2 (Pfizer/BioNTech) is a coronavirus disease 2019 (COVID-19) vaccine containing nucleoside-modified messenger RNA encoding the severe acute respiratory syndrome coronavirus 2 spike glycoprotein. Recently, ocular complications of mRNA vaccines have been reported increasingly frequently. However, immunological adverse events due to mRNA vaccines in real-world settings are not fully known. We herein report the novel development of sarcoidosis manifested as uveitis, bilateral hilar lymphadenopathy, angiotensin-converting enzyme elevation, and epithelioid and giant cell granuloma formation in the lung soon after the first BNT162b2 injection and review the current literature, including three reported cases of sarcoid-like reaction following COVID-19 vaccination.

Genetic loci for lung function in Japanese adults with adjustment for exhaled nitric oxide levels as airway inflammation indicator.

Lung function reflects the ability of the respiratory system and is utilized for the assessment of respiratory diseases. Because type 2 airway inflammation influences lung function, genome wide association studies (GWAS) for lung function would be improved by adjustment with an indicator of the inflammation. Here, we performed a GWAS for lung function with adjustment for exhaled nitric oxide (FeNO) levels in two independent Japanese populations. Our GWAS with genotype imputations revealed that the RNF5/AGER locus including AGER rs2070600 SNP, which introduces a G82S substitution of AGER, was the most significantly associated with FEV1/FVC. Three other rare missense variants of AGER were further identified. We also found genetic loci with three candidate genes (NOS2, SPSB2 and RIPOR2) associated with FeNO levels. Analyses with the BioBank-Japan GWAS resource revealed genetic links of FeNO and asthma-related traits, and existence of common genetic background for allergic diseases and their biomarkers. Our study identified the genetic locus most strongly associated with airway obstruction in the Japanese population and three genetic loci associated with FeNO, an indicator of type 2 airway inflammation in adults.

Upregulation of leukocyte immunoglobulin-like receptor B4 on interstitial macrophages in COPD; their possible protective role against emphysema formation.

BACKGROUND: Leukocyte immunoglobulin-like receptor B4 (LILRB4) is one of the inhibitory receptors in various types of immune cells including macrophages. Previous reports suggested that LILRB4 could be involved in a negative feedback system to prevent excessive inflammatory responses. However, its role has been unclear in chronic obstructive pulmonary disease (COPD), in which macrophages play a crucial role in the pathogenesis. In this study, we aimed to examine the changes of LILRB4 on macrophages both in the lung specimens of COPD patients and the lungs of a mouse emphysema model. We then tried to compare the differences in both inflammation and emphysematous changes of the model between wild-type and LILRB4-deficient mice in order to elucidate the role of LILRB4 in the pathogenesis of COPD. METHODS: We prepared single-cell suspensions of resected lung specimens of never-smokers (n = 21), non-COPD smokers (n = 16), and COPD patients (n = 14). The identification of LILRB4-expressing cells and the level of LILRB4 expression were evaluated by flow cytometry. We analyzed the relationships between the LILRB4 expression and clinical characteristics including respiratory function. In the experiments using an elastase-induced mouse model of emphysema, we also analyzed the LILRB4 expression on lung macrophages. We compared inflammatory cell accumulation and emphysematous changes induced by elastase instillation between wild-type and LILRB4-deficient mice. RESULTS: The levels of surface expression of LILRB4 are relatively high on monocyte linage cells including macrophages in the human lungs. The percentage of LILRB4+ cells in lung interstitial macrophages was increased in COPD patients compared to non-COPD smokers (p = 0.018) and correlated with the severity of emphysematous lesions detected by CT scan (rs = 0.559, p < 0.001), whereas the amount of smoking showed no correlation with LILRB4 expression. Increased LILRB4 on interstitial macrophages was also observed in elastase-treated mice (p = 0.008). LILRB4-deficient mice showed severer emphysematous lesions with increased MMP-12 expression in the model. CONCLUSIONS: LILRB4 on interstitial macrophages was upregulated both in human COPD lungs and in a mouse model of emphysema. This upregulated LILRB4 may have a protective effect against emphysema formation, possibly through decreasing MMP-12 expression in the lungs.

[A CASE OF BRONCHIAL ASTHMA IN A YOUNGER PATIENT WITH VOCAL CORD DYSFUNCTION].

We present a case of a 17-year-old woman with a history of bronchial asthma since two years of age. She had daily asthma attacks from the age of fourteen, and the addition of oral corticosteroids and omalizumab to regular inhaled corticosteroid inhalation failed to relieve symptoms. She was referred to our hospital for detailed examination. On admission, physical examination was normal, but she had complained of dyspnea at the round. Monophonic wheezes and stridor were heard over the anterior neck, while no rales were audible over any part of the chest. Laryngoscopy revealed paradoxical movement of the vocal cords, and a diagnosis of vocal cord dysfunction (VCD) was made. The apparent severe asthma symptoms were considered to reflect VCD, and the treatment for bronchial asthma was stepped down without any recurrence of asthma attacks. Although the etiology of the VCD was unknown, VCD is more common in young women, so stress and personality factors are thought to be involved. It has been noted that childhood asthma often improves between childhood and adolescence, but refractory cases have been noted. In intractable bronchial asthma cases, it is necessary to consider the complications of other diseases, such as VCD, and to perform appropriate management.

Nitrosative stress in patients with asthma-chronic obstructive pulmonary disease overlap.

BACKGROUND: Asthma-chronic obstructive pulmonary disease overlap (ACO) has frequent exacerbations and a poor quality of life and prognosis compared with those of chronic obstructive pulmonary disease alone. However, the pathogenesis of ACO has not been fully elucidated yet. OBJECTIVES: The aim of this study was to investigate nitrosative stress, which causes a redox imbalance and tissue inflammation in the airways of patients with ACO, and to evaluate the relationship between nitrosative stress and the clinical course in study subjects. METHODS: Thirty healthy subjects and 56 asthmatic patients participated in this study. The asthmatic patients were divided into 33 asthmatic patients and 23 patients with ACO. The study subjects had been followed prospectively for 2 years to evaluate the clinical course. Nitrosative stress was evaluated based on the production of 3-nitrotyrosine (3-NT) in sputum cells. RESULTS: Production of 3-NT was significantly enhanced in patients with ACO compared with that in asthmatic patients. Amounts of reactive persulfides and polysulfides, newly identified powerful antioxidants, were significantly decreased in the ACO group. Baseline levels of 3-NT were significantly correlated with the frequency of exacerbations and decrease in FEV1 adjusted by age, smoking history, and blood eosinophil count. The 3-NT-positive cells were also significantly correlated with amounts of proinflammatory chemokines and cytokines. CONCLUSIONS: These findings suggested that greater nitrosative stress occurred in the airways of patients with ACO, and the degree of nitrosative stress was correlated with an impairment in the clinical course. Nitrosative stress might be related to the pathogenesis of ACO.

Relapsed Myasthenia Gravis after Nivolumab Treatment.

Nivolumab is a newly introduced promising therapy for treating lung cancer that restores the anti-tumor immunity by disrupting programmed cell death-1-mediated immuno-suppressive signaling. Although "new-onset" autoimmune diseases are well-known immune-related adverse events, whether or not nivolumab exacerbates "pre-existing" autoimmune disease remains unclear. We herein report a patient with "pre-existing" myasthenia gravis in whom nivolumab was administered that flared up after the treatment with nivolumab. Regardless of the disease stability, nivolumab has the potential to exacerbate an autoimmune disease, and we must pay close attention to each patient's medical history before administering this agent.