Multi-Nodule of Large Airway: Tracheobronchopathia Osteochondroplastica, Two Cases Report and Literature Review

We report two subjects with tracheobronchopathia osteochondroplastica (TO), including the clinical manifestations, histological findings, and clinical treatments, which were analyzed retrospectively. One patient with TO was a 60-year-old woman, and the other was a 47-year-old man. The main clinical manifestations were cough, chest pain, and dyspnea. Computed tomography (CT) images showed that TO mainly occurred in the trachea and main bronchus. Histological analysis showed inflammatory exudation, squamous metaplasia, submucosal cartilaginous, and ossification. We present the two cases to increase physician and patient awareness of this benign disease and to improve their understanding of the disease manifestations and potential complications.

Pediatric anterior larynx: presentations and associations

Objective: The literature on the entity of the anterior larynx (AL) is restricted to little evidence on the difficulty encountered in exposing the larynx for intubation, perioperative morbidity and mortality, and scant reports on its prevalence in general adults and children. We here describe the prevalence of AL in a series of children presenting with aerodigestive symptoms and explore its association with functional abnormalities, congenital and structural anomalies or conditions. Setting: Tertiary pediatric center Methods: we conducted a retrospective case-control study. Using a prospectively collected surgical database we identified patients diagnosed with AL (grades IIb-III-IV Modified Cormack-Lehane scale) and sex and age-matched controls who had undergone full airway endoscopy for aerodigestive symptoms. We collected the demographics, presentations, associated diagnoses, and investigations. We compared the proportion of patients with large airway abnormalities and dysmorphism and estimated the prevalence of AL. Results: over a 5.5-year period, 58 children (28 females) were matched with 58 controls. Although both groups presented with permutations of stridor, respiratory failure, cyanotic spells, swallowing and feeding difficulties and SDB, AL presented much more with swallowing and feeding problems (33 vs 20, p<0.05). There were significantly more children with dysmorphism in the AL group (29 vs 9, P < 0.05). The prevalence of AL was 4.9%. Conclusions: This is the first study to report the prevalence of AL amongst a cohort of children with aerodigestive symptoms. Its significant association with dysmorphic features warrants genetic consultation. It is associated with swallowing abnormalities that justifies a systematic instrumental evaluation

Large airway complications in COVID-19 pneumonia

COVID-19 pneumonia can cause respiratory failure which requires specialist management. However the inflammatory nature of the condition and the interventions necessary to manage these patients such as endotracheal intubation and tracheostomy can lead to large airway pathology which may go unrecognised. We describe five of the 44 (11%) consecutive patients referred to our specialist ARDS team between April and June 2020 with confirmed COVID-19 pneumonia who developed diverse large airway pathology which comprised of: supraglottic oedema, tracheal tear, tracheal granulation tissue formation, bronchomalacia, and tracheal diverticulum. Large airway pathology may be underappreciated in severely ill patients with COVID-19 pneumonia and should be considered in patients with unexplained air leak, prolonged need for mechanical ventilatory support, and repeated failed extubation or decannulation. If suspected, such patients should be managed by a team with expertise in large airway intervention and early specialist advice should be sought.

Detection and diagnosis of large airway collapse: a systematic review

Large airway collapse (LAC) is a frequently encountered clinical problem, caused by tracheobronchomalacia +/- excessive dynamic airway collapse, yet there are currently no universally accepted diagnostic criteria. We systematically reviewed studies reporting a diagnostic approach to LAC in healthy adults and patients, to compare diagnostic modalities and criteria used. Electronic databases were searched for relevant studies between 1989 and 2019. Studies that reported a diagnostic approach using computed tomography (CT), magnetic resonance imaging, or flexible fibreoptic bronchoscopy were included. Random effects meta-analyses were performed to estimate the prevalence of LAC in healthy subjects and in patients with chronic obstructive airway diseases. We included 41 studies, describing 10,071 subjects (47% female), and mean (+/- sd) age 59±9 years. Most studies (n=35) reported CT findings and only 3 studies report bronchoscopic findings. The most reported diagnostic criterion was a ≥50% reduction in tracheal or main bronchi calibre at end-expiration on dynamic expiratory CT. Meta-analyses of relevant studies found that 17% (95% CI: 0–61%) of healthy subjects and 27% (95% CI: 11–46%) of patients with chronic airways disease were classified as having LAC, using this threshold. The most reported approach to diagnose LAC utilises CT diagnostics and at a threshold used by most clinicians (i.e., ≥50%) may classify a considerable proportion of healthy individuals as being abnormal and LAC in a quarter of patients with chronic airways disease. Future work should focus on establishing more precise diagnostic criteria for LAC, relating this to relevant physiological and disease sequalae.

Feasibility of an Inhalable Ultrasound Contrast Agent to Enhance Airway Imaging

Introduction: Ultrasound is a relatively inexpensive and non-ionizing imaging modality, but is under-utilized in large airway assessments due to poor image quality. No commercially available contrast agents currently exist for sonographic evaluation of the respiratory system, nor has a respiratory route of microbubble contrast agent (MCA) administration been previously described for the enhancement of airway imaging. Methods: We conducted a feasibility study to assess proof-of-concept for an inhalable ultrasound MCA composed of lipid-encapsulated decaflourobutane gas. The MCA was nebulized and administered as an aerosol through the lumen of an ex vivo porcine trachea, with image enhancement evaluated by comparing images pre- and post-exposure. Additionally, primary human bronchial epithelial (hBE) cells from three donors were differentiated at an air-liquid interface and exposed apically to 25 μL of undiluted MCA or vehicle control to assess contrast agent-induced cytotoxicity and inflammation. Basolateral medium was collected 24-hours post-exposure and lactate dehydrogenase (LDH) and interleukin-8 (IL-8) concentrations were measured as biomarkers of cytotoxicity and inflammation, respectively. Results: Contrast microbubbles remained intact following nebulization and enhanced sonographic delineation of ex vivo porcine tracheal walls, indicating adherence of the nebulized MCA to the lumenal mucosa. No significant cytotoxic or inflammatory effects were observed in cultured hBE cells following exposure to MCA. Conclusions: We present proof-of-concept for an inhaled MCA for the enhancement of sonographic evaluations of the large airways. Pending further safety and efficacy evaluations, inhaled MCA may be feasible for clinical ultrasound applications, such as enhancing ultrasound-guided tracheal intubation, detecting airway bleeds, or monitoring large airway diseases in pediatric populations.

Endobronchial actinomycosis in a child during COVID-19 pandemic

Actinomycosis is a rare, indolent and invasive infection caused by Actinomyces species. Pulmonary actinomycosis is very rarely seen in the paediatric population. The classic radiological presentation of thoracic involvement of actinomycosis includes lower lobe consolidation, empyema and periostitis of the ribs. We report a case of endobronchial pulmonary actinomycosis in a child diagnosed on endobronchial biopsy and broncho-alveolar lavage taken during bronchoscopy. Bronchoscopy can be dangerous when performed on these cases, as there is a risk of severe bleeding and large airway obstruction, as was the case with this patient.

Genetic and non-genetic factors affecting the expression of COVID-19-relevant genes in the large airway epithelium

Background The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be partially mediated by the differential regulation of the genes that interact with the SARS-CoV-2 virus or are involved in the subsequent host response. Here, we comprehensively investigated non-genetic and genetic factors influencing COVID-19-relevant bronchial epithelial gene expression. Methods We analyzed RNA-sequencing data from bronchial epithelial brushings obtained from uninfected individuals. We related ACE2 gene expression to host and environmental factors in the SPIROMICS cohort of smokers with and without chronic obstructive pulmonary disease (COPD) and replicated these associations in two asthma cohorts, SARP and MAST. To identify airway biology beyond ACE2 binding that may contribute to increased susceptibility, we used gene set enrichment analyses to determine if gene expression changes indicative of a suppressed airway immune response observed early in SARS-CoV-2 infection are also observed in association with host factors. To identify host genetic variants affecting COVID-19 susceptibility in SPIROMICS, we performed expression quantitative trait (eQTL) mapping and investigated the phenotypic associations of the eQTL variants. Results We found that ACE2 expression was higher in relation to active smoking, obesity, and hypertension that are known risk factors of COVID-19 severity, while an association with interferon-related inflammation was driven by the truncated, non-binding ACE2 isoform. We discovered that expression patterns of a suppressed airway immune response to early SARS-CoV-2 infection, compared to other viruses, are similar to patterns associated with obesity, hypertension, and cardiovascular disease, which may thus contribute to a COVID-19-susceptible airway environment. eQTL mapping identified regulatory variants for genes implicated in COVID-19, some of which had pheWAS evidence for their potential role in respiratory infections. Conclusions These data provide evidence that clinically relevant variation in the expression of COVID-19-related genes is associated with host factors, environmental exposures, and likely host genetic variation.