Pediatric obstructive sleep apnea (OSA) is a syndrome manifesting with snoring and increased respiratory effort due to increased upper airway resistance. In addition to cause the abnormal sleep, this syndrome has been shown to elicit either growth retardation or metabolic syndrome and obesity. Treating OSA by adenotonsillectomy is usually associated with increased risk for obesity, despite near complete restoration of breathing and sleep. However, the underlying mechanism linking upper airways obstruction (AO) to persistent change in food intake, metabolism, and growth remains unclear. Rodent models have examined the impact of intermittent hypoxia on metabolism. However, an additional defining feature of OSA that is not related to intermittent hypoxia is enhanced respiratory loading leading to increased respiratory effort and abnormal sleep. The focus of this mini review is on recent evidence indicating the persistent abnormalities in endocrine regulation of feeding and growth that are not fully restored by the chronic upper AO removal in rats. Here, we highlight important aspects related to abnormal regulation of metabolism that are not related to intermittent hypoxia per se, in an animal model that mimics many of the clinical features of pediatric OSA. Our evidence from the AO model indicates that obstruction removal may not be sufficient to prevent the post-removal tendency for abnormal growth.

Subglottic hemangioma is a rare benign tumor in children. It causes an obstruction of the upper airway and can be life-threatening. Several therapeutic options have been used in the literature, including surgery. Currently, the treatment is essentially based on propranolol. We report the case of a 2-month-old female infant hospitalized for severe obstructive dyspnea secondary to a subglottic hemangioma. Diagnosis was confirmed by laryngoscopy and magnetic resonance imaging. The child underwent a tracheotomy and was treated with propranolol. The progression was favorable with regression of the subglottic hemangioma and improvement of laryngotracheal airway obstruction.

Obstructive sleep apnea (OSA) is a common disorder characterized by episodic obstruction to breathing due to upper airway collapse during sleep. Because of the episodic airway obstruction, intermittently low O2 (hypoxia) and high CO2 (hypercapnia) ensue. OSA has been associated with adverse cardiovascular and metabolic outcomes, although data regarding potential causal pathways are still evolving. As changes in inspired O2 and CO2 can affect the ecology of the gut microbiota and the microbiota has been shown to contribute to various cardiometabolic disorders, we hypothesized that OSA alters the gut ecosystem, which, in turn, exacerbates the downstream physiological consequences. Here, we model human OSA and its cardiovascular consequence using Ldlr-/- mice fed a high-fat diet and exposed to intermittent hypoxia and hypercapnia (IHH). The gut microbiome and metabolome were characterized longitudinally (using 16S rRNA amplicon sequencing and untargeted liquid chromatography-tandem mass spectrometry [LC-MS/MS]) and seen to covary during IHH. Joint analysis of microbiome and metabolome data revealed marked compositional changes in both microbial (>10%, most remarkably in Clostridia) and molecular (>22%) species in the gut. Moreover, molecules that altered in abundance included microbe-dependent bile acids, enterolignans, and fatty acids, highlighting the impact of IHH on host-commensal organism cometabolism in the gut. Thus, we present the first evidence that IHH perturbs the gut microbiome functionally, setting the stage for understanding its involvement in cardiometabolic disorders. IMPORTANCE Intestinal dysbiosis mediates various cardiovascular diseases comorbid with OSA. To understand the role of dysbiosis in cardiovascular and metabolic disease caused by OSA, we systematically study the effect of intermittent hypoxic/hypercapnic stress (IHH, mimicking OSA) on gut microbes in an animal model. We take advantage of a longitudinal study design and paired omics to investigate the microbial and molecular dynamics in the gut to ascertain the contribution of microbes on intestinal metabolism in IHH. We observe microbe-dependent changes in the gut metabolome that will guide future research on unrecognized mechanistic links between gut microbes and comorbidities of OSA. Additionally, we highlight novel and noninvasive biomarkers for OSA-linked cardiovascular and metabolic disorders.

We present a case of a 76 year-old, non-smoking Honduran female who was referred to our clinic for years of persistent dry cough. Cardiac evaluation was unremarkable. She denied symptoms of heartburn, allergic rhinitis, and there was no personal or family history of asthma. Her physical exam demonstrated wheezing over the right mid-posterior chest. Spirometry was within normal limits. CT-imaging of the chest demonstrated right middle lobe bronchus and lingular segmental bronchus narrowing with bibasilar atelectasis and mild interlobular septal thickening with prominent mediastinal adenopathy. Bronchoscopy showed diffuse airway hyperpigmentation, right middle lobe medial segmental bronchial stenosis and lingular segmental bronchial stenosis. Endobronchial ultrasound demonstrated enlarged mediastinal lymph nodes, and transbronchial needle aspirates revealed necrotic tissue with black anthracotic pigment. Cultures were negative. Post-procedurally, the patient revealed regular use of a wood stove in an enclosed, poorly-ventilated kitchen. Anthracosis is the black discoloration of bronchial mucosa due to deposition of carbon-based particles in the airway, usually related to chronic environmental exposures. It can eventually result in endobronchial and parenchymal fibrosis and is mostly seen in non-smokers. Burning biomass fuel from wood smoke is a risk factor in the developing world. Symptoms include cough, dyspnea, and wheezing. Spirometry will usually demonstrate obstruction. CT-based imaging can show intraluminal narrowing, predominantly affecting the right middle and right upper lobe bronchi, resulting in distal segmental collapse. Extrapulmonary findings are rare, but usually are in the form of calcified mediastinal adenopathy on CT-based imaging, which allows for differentiation from lung cancer. There is no reliable treatment though bronchodilators can achieve clinical benefit.

Development of effective rescue countermeasures for toxic inhalational industrial chemicals, such as methyl isocyanate (MIC), has been an emerging interest. Nonetheless, current methods for studying toxin-induced airway injuries are limited by cost, labor time, or accuracy, and only provide indirect or localized information. Optical Coherence Tomography (OCT) endoscopic probes have previously been used to visualize the 3-D airway structure. However, gathering such information in small animal models, such as rat airways after toxic gas exposure, remains a challenge due to the required probe size necessary for accessing the small, narrow, and partially obstructed tracheas. In this study, we have designed a 0.4 mm miniature endoscopic probe and investigated the structural changes in rat trachea after MIC inhalation. An automated 3D segmentation algorithm was implemented so that anatomical changes, such as tracheal lumen volume and cross-sectional areas, could be quantified. The tracheal region of rats exposed to MIC by inhalation showed significant airway narrowing, especially within the upper trachea, as a result of epithelial detachment and extravascular coagulation within the airway. This imaging and automated reconstruction technique is capable of rapid and minimally-invasive identification of airway obstruction. This method can be applied to large-scale quantitative analysis of in vivo animal models.