Background: Sarcopenia and frailty are highly prevalent extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD) and are strongly associated with reduced exercise tolerance, exacerbation risk, hospitalizations, and mortality. Beyond inflammation, oxidative stress, and physical inactivity, emerging evidence highlights nutrition as a major modifiable driver of muscle deterioration in COPD. Nutritional deficits impair anabolic signaling, exacerbate proteolysis, worsen mitochondrial dysfunction, and contribute to frailty progression. Methods: This narrative review synthesizes evidence from PubMed, Embase, Scopus, and Web of Science up to 2025, integrating mechanistic, metabolic, nutritional, and biomarker-related pathways underlying muscle dysfunction in COPD. Studies examining inflammation, hypoxemia, oxidative stress, hormonal imbalance, nutrition, and emerging biomarkers were included. Results: COPD-related sarcopenia results from converging inflammatory (TNF-α, IL-6), catabolic (FOXO, UPS), metabolic, and vascular mechanisms, compounded by energy deficiency, protein insufficiency, and micronutrient deficits. Inadequate intake of protein, vitamin D, antioxidants, and omega-3 fatty acids increase anabolic resistance, enhance muscle catabolism, and worsen frailty. Nutritional interventions, particularly high-protein supplementation, leucine-enriched formulas, vitamin D repletion, omega-3 fatty acids, and multimodal nutrition–exercise programs, demonstrate benefits in muscle mass, strength, and physical performance. Biomarkers such as GDF-15, CAF22, and specific microRNAs reflect nutritional status and correlate with muscle health in COPD. Conclusions: Sarcopenia and frailty in COPD arise from a complex interplay of inflammatory, metabolic, nutritional, and lifestyle-related factors. Integrating nutritional assessment and targeted dietary interventions with exercise and pulmonary rehabilitation is essential to counteract anabolic resistance and improve functional outcomes. Advances in biomarker research may support earlier diagnosis and personalized nutrition-based therapeutic strategies.

Background: Primary immunodeficiencies (PID) are rare disorders of the immune system encompassing inborn errors of immunity leading to pulmonary complications frequently, which may affect exercise capacity. The impact of varying exercise intensities on muscle oxygenation is questioned. This study aims to compare muscle oxygenation during the 6-minute walk (6MWT) and cardiopulmonary exercise tests (CPET) in patients with PID. Methods: A cross-sectional study. Ten children with PID (9-13 y) were included. Pulmonary function (spirometer), and quadriceps femoris (QF) muscle strength using a handheld dynamometer were evaluated. Muscle oxygen saturation and total hemoglobin levels were measured (near infrared spectroscopy (NIRS) device) during CPET and 6MWT. Results: Muscle saturation at rest, minimal and maximal during exercise and recovery, were similar during the CPET and 6MWT (p>0.05). Meanwhile, THbmax and THbrecovery were higher during CPET with significant difference (p<0.05). 90% of patients had 6MWD, 60% had VO_2max and 50% had QF muscle strength less than 80% of expected. Also, 40% had obstructive pulmonary function abnormality. Conclusions: The majority of the patients had impaired functional and maximal exercise capacity. Nearly half of the patients had obstructive pulmonary function and QF muscle weakness. Muscle oxygen saturation responses were similar during submaximal and maximal tests, however THb levels exhibit elevated during CPET. These findings highlight the importance of a proactive approach to address multifaceted challenges faced by patients with PID. The effects of pulmonary rehabilitation in patients with PID needs to be investigated.

Background: Inborn Errors of Immunity (IEI) are rare disorders caused by defects in the immune system. Increased susceptibility to infections and chronic pulmonary complications often impair overall health. The impact of IEI on exercise capacity remains poorly understood. This study aimed to compare maximal exercise capacity, pulmonary function, physical activity, quality of life, and muscle oxygenation in patients with IEI and healthy controls. Methods: Eighteen patients with IEI and 15 healthy children were evaluated. Measurements included incremental ramp cardiopulmonary exercise testing (CPET), spirometry, physical activity monitoring (SenseWear), quality of life (PedsQL), and muscle oxygenation via Near-Infrared Spectroscopy (NIRS). Results: No significant differences were found between groups in FVC, FEV₁, PEF, and FEF_25-75% (p>0.05). However, patients with IEI exhibited significantly lower peakVO₂, peakVO_2kg, total energy expenditure, active energy expenditure, daily step count, and average MET values (p<0.05). During CPET, patients demonstrated significantly lower SmO_2rest, SmO_2max, SmO_2avg-max(p<0.05). Furthermore, patients reported significantly lower scores for psychosocial health, physical health, and total PedsQL (p<0.05). Conclusions: Children with IEI exhibit impaired maximal exercise capacity, reduced quality of life and decreased physical activity levels despite preserved pulmonary function. The reduction in muscle oxygenation suggests that peripheral oxygen utilization may be a limiting factor. Routine evaluation of extra-pulmonary manifestations is essential to optimize personalized care and rehabilitation strategies for this population.