Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems

Abstract

BackgroundRepetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase‐3, followed by further degradation by the ubiquitin‐proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle. For swallowing muscles, it is not clear whether they produce cytokines. The main objective of this study was to determine whether aspiration pneumonia induces muscle atrophy in the respiratory (the diaphragm), skeletal (the tibialis anterior, TA), and swallowing (the tongue) systems, and their possible mechanisms.MethodsWe employed a mouse aspiration pneumonia model and computed tomography (CT) scans of aged pneumonia patients. To induce aspiration pneumonia, mice were inoculated with low dose pepsin and lipopolysaccharide solution intra‐nasally 5 days a week. The diaphragm, TA, and tongue were isolated, and total RNA, proteins, and frozen sections were stored. Quantitative real‐time polymerase chain reaction determined the expression levels of proinflammatory cytokines, muscle E3 ubiquitin ligases, and autophagy related genes. Western blot analysis determined the activation of the muscle proteolysis pathway. Frozen sections determined the presence of muscle atrophy. CT scans were used to evaluate the muscle atrophy in aged aspiration pneumonia patients.ResultsThe aspiration challenge enhanced the expression levels of proinflammatory cytokines in the diaphragm, TA, and tongue. Among muscle proteolysis pathways, the aspiration challenge activated caspase‐3 in all the three muscles examined, whereas calpains were activated in the diaphragm and the TA but not in the tongue. Activation of the ubiquitin‐proteasome system was detected in all the three muscles examined. The aspiration challenge activated autophagy in the TA and the tongue, whereas weak or little activation was detected in the diaphragm. The aspiration challenge resulted in a greater proportion of smaller myofibers than in controls in the diaphragm, TA, and tongue, suggesting muscle atrophy. CT scans clearly showed that aspiration pneumonia was followed by muscle atrophy in aged patients.ConclusionsAspiration pneumonia induced muscle atrophy in the respiratory, skeletal, and swallowing systems in a preclinical animal model and in human patients. Diaphragmatic atrophy may weaken the force of cough to expectorate sputum or mis‐swallowed contents. Skeletal muscle atrophy may cause secondary sarcopenia. The atrophy of swallowing muscles may weaken the swallowing function. Thus, muscle atrophy could become a new therapeutic target of aspiration pneumonia.

Sarcopenia is associated with tongue pressure in older patients with type 2 diabetes: A cross‐sectional study of the KAMOGAWA‐DM cohort study

“…8 However, when we identify patients with sarcopenia, especially those with low hand handgrip strength, we should be aware of the possibility of future risk of aspiration pneumonia, because low tongue pressure is associated with the risk of aspiration pneumonia. 28 We should mention the limitations of the present study. First, we used a mulitifrequency impedance method for body composition, although the gold standard test is dual-energy X-ray absorptiometry.…”

“…Low tongue pressure is not equal to swallowing dysfunction, because swallowing function consists of several components, such as bite force, swallowing muscle mass and swallowing muscle quality . However, when we identify patients with sarcopenia, especially those with low hand handgrip strength, we should be aware of the possibility of future risk of aspiration pneumonia, because low tongue pressure is associated with the risk of aspiration pneumonia …”

Sarcopenia and dysphagia: Position paper by four professional organizations

“…Furthermore, head‐raising exercises and muscle strengthening exercises of the tongue are known to improve swallowing function. In 2018, a basic research study by Komatsu et al found that aspiration pneumonia accentuated muscular decomposition and induced muscular atrophy in the tongue and diaphragm . In addition, atrophy was found in the respiratory muscles, skeletal muscles of the body and swallowing muscles .…”

“…In addition, under sarcopenia, it is difficult for an older person to maintain an appropriate posture for swallowing by controlling his/her skeletal muscles and subglottic air pressure. Likewise, it is difficult to maintain the respiratory functions necessary to cough out sputum and/or aspirated materials . Needless to say, the concept of holistic rehabilitation, including posture, is important when treating dysphagia.…”

“…32 In addition, atrophy was found in the respiratory muscles, skeletal muscles of the body and swallowing muscles. 32 On the basis of these findings, there is an urgent need for the accumulation of clinical and scientific evidence pertaining to the potential revocability of sarcopenia by nutritional improvement and exercises, and the differences between sarcopenia and disuse in terms of atrophy and muscular dysfunction. In addition, further investigations are necessary to clarify whether the uniqueness of the swallowing muscles with/without branchial origin is associated with greater resistance against age-related changes than that observed in general somatic muscles.…”