Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early discrimination of macrolide-refractory M. pneumoniae pneumonia (MrMP) from macrolide-sensitive M. pneumoniae pneumonia (MSMP) is vital; however, testing for macrolide susceptibility at the time of admission is not feasible. This study aimed to identify the characteristics of MrMP in Korean children, in comparison with those of MSMP. In this multicenter study, board-certified pediatric pulmonologists at 22 tertiary hospitals reviewed the medical records from 2010 to 2015 of 5294 children who were hospitalized with M. pneumoniae pneumonia and administered macrolides as the initial treatment. One-way analysis of variance and the Kruskal-Wallis test were used to compare differences between groups. Of 5294 patients (mean age, 5.6 years) included in this analysis, 240 (4.5%), 925 (17.5%), and 4129 (78.0%) had MrMP, macrolide-less effective M. pneumoniae pneumonia, and MSMP, respectively. Compared with the MSMP group, the MrMP group had a longer fever duration, overall (13.0 days) and after macrolide use (8.0 days). A higher proportion of MrMP patients had respiratory distress, pleural effusion, and lobar pneumonia. The mean aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein levels were the highest in the MrMP group, along with higher incidences of extrapulmonary manifestations and atelectasis (during and post infection). Pre-existing conditions were present in 17.4% (n = 725/4159) of patients, with asthma being the most common (n = 334/4811, 6.9%). This study verified that MrMP patients show more severe initial radiographic findings and clinical courses than MSMP patients. MrMP should be promptly managed by agents other than macrolides.

Lactate, once regarded as a metabolic byproduct, is now recognized as a critical immunometabolic regulator that shapes immune responses in both physiological and pathological contexts. This review examines how lactate accumulation occurs across diverse disease settings, including cancer, sepsis, and diabetes, through mechanisms such as hypoxia, mitochondrial dysfunction, and pharmacologic intervention. We then explore how lactate modulates immunity via four integrated mechanisms: transporter-mediated flux, receptor signaling (e.g., GPR81), context-dependent metabolic rewiring, and histone/protein lactylation. Particular emphasis is placed on the dichotomous effects of endogenous versus exogenous lactate, with the former supporting glycolytic effector functions and the latter reprogramming immune cells toward regulatory phenotypes via redox shifts and epigenetic remodeling. The review also highlights how the directionality of lactate transport, and the metabolic readiness of the cell determine, whether lactate sustains inflammation or promotes resolution. After analyzing emerging data across immune cell subsets and disease contexts, we propose that lactate serves as a dynamic rheostat that integrates environmental cues with intracellular metabolic and epigenetic programming. Understanding these context-dependent mechanisms is essential for the rational design of lactate-targeted immunotherapies that aim to modulate immune responses without disrupting systemic homeostasis.

Kim M, et al. Allergy Asthma Immunol Res. 2023 Nov;15(6):757-766. https://doi.org/10.4168/aair.2023.15.6.757

Background: Bronchial hyperresponsiveness (BHR), an important physiological feature of asthma, is a prognostic marker of childhood asthma.Purpose: We aimed to investigate the factors associated with BHR in adolescents with childhood asthma.Methods: Two hundred and fifteen adolescents (≥13 years of age; 149 males, 66 females) who were diagnosed with asthma during childhood were enrolled, underwent methacholine challenge tests, and were divided into the BHR group (<25 mg/mL of provocation concentration causing a 20% fall in forced expiratory volume in 1 second [FEV1] [PC20], n=113) or non-BHR group (≥25 mg/mL of PC20, n=102). We examined longitudinal changes in BHR and the risk factors for its persistence in the 108 adolescents for whom baseline data, including methacholine PC20 at age 6 years, were available. Multivariate logistic regression analyses were performed to assess the factors associated with BHR in adolescents.Results: Mold sensitization (adjusted odds ratio [aOR], 5.569; P=0.005) and increased blood eosinophil count (aOR, 1.002; P=0.026) were independently associated with BHR in boys but not girls. The odds of BHR decreased by 32% with each 1-year increase in age in boys (aOR, 0.683; P=0.010) but not girls. A reduced FEV1/forced vital capacity ratio (<90%) was independently related with BHR in female patients only (aOR, 7.500; P=0.007). BHR decreased with age throughout childhood. A low methacholine PC20 at age 6 years was independently associated with persistent BHR throughout childhood in male and female patients, whereas early mold sensitization was a risk factor for persistent BHR in male patients only (aOR, 7.718; P=0.028).Conclusion: Our study revealed sex-specific differences in the factors associated with BHR in adolescents with childhood asthma. Our findings suggest the risk factors that might affect asthma transition from childhood to adolescence and adulthood.

Fractional exhaled nitric oxide (FeNO) is a non-invasive test for evaluating the degree of airway inflammation and for the diagnosis, evaluation, and treatment of asthma. We attempted to measure FeNO levels in Korean children with asthma and determine its cutoff value for diagnosing asthma. We enrolled 176 children and adolescents between the ages of 5 and 18 years, who visited for the evaluation of chronic cough, shortness of breath, and wheezing. Among them, 138 patients who underwent skin prick tests or inhalation Immuno CAP (UniCAP; Pharmacia, Uppsala, Sweden) tests for allergy testing together with a pulmonary function test were included. FeNO was measured using a NIOX MINO (Aerocrine AB, Solna, Sweden) instrument according to the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. There were 29 patients with asthma, 43 with rhinitis, and 38 with asthma and allergic rhinitis. In the asthma group, FeNO levels significantly correlated with total immunoglobulin E (r = 0.572, p < 0.001), but did not show significant correlation with pulmonary function test parameters (forced vital capacity—FVC, forced expiratory volume in one second—FEV1, FEV1/FVC) or PC20 (provocative concentration of methacholine causing a 20% fall in FEV1). The FeNO cutoff values obtained in the asthma and asthma rhinitis groups were 16.5 ppb and 18.5 ppb, respectively. Hence, we provide a FeNO cutoff value according to the presence or absence of rhinitis in pediatric patients with asthma.