Airway necrosis and granulation tissue formation caused by Rhizopus oryzae leading to severe upper airway obstruction: a case report.

Pulmonary Mucormycosis is a fatal infectious disease with high mortality rate. The occurrence of Mucormycosis is commonly related to the fungal virulence and the host's immunological defenses against pathogens. Mucormycosis infection and granulation tissue formation occurred in the upper airway was rarely reported. This patient was a 60-year-old male with diabetes mellitus, who was admitted to hospital due to progressive cough, sputum and dyspnea. High-resolution computed tomography (HRCT) and bronchoscopy revealed extensive tracheal mucosal necrosis, granulation tissue proliferation, and severe airway stenosis. The mucosal necrotic tissue was induced by the infection of Rhizopus Oryzae, confirmed by metagenomic next-generation sequencing (mNGS) in tissue biopsy. This patient was treated with the placement of a covered stent and local instillation of amphotericin B via bronchoscope. The tracheal mucosal necrosis was markedly alleviated, the symptoms of cough, shortness of breath, as well as exercise tolerance were significantly improved. The placement of airway stent and transbronchial microtube drip of amphotericin B could conduce to rapidly relieve the severe airway obstruction due to Mucormycosis infection.

miR-34c-5p inhibited fibroblast proliferation, differentiation and epithelial-mesenchymal transition in benign airway stenosis via MDMX/p53 pathway.

Benign airway stenosis (BAS) means airway stenosis or obstruction that results from a variety of non-malignant factors, including tuberculosis, trauma, benign tumors, etc. In consideration of the currently limited research on microRNAs in BAS, this study aimed to explore the role and mechanism of miR-34c-5p in BAS. The expression of miR-34c-5p in BAS granulation tissues showed a significant down-regulation compared with the normal control group. Moreover, miR-34c-5p mimics suppressed the proliferation and differentiation of human bronchial fibroblasts (HBFs) and the epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBE). Conversely, miR-34c-5p inhibitors aggravated those effects. A dual-luciferase reporter assay confirmed that miR-34c-5p can target MDMX rather than Notch1. The over-expression of MDMX can reverse the inhibiting effect of miR-34c-5p on HBFs proliferation, differentiation and EMT. Furthermore, the expressions of tumor protein (p53) and PTEN were down-regulated following the over-expression of MDMX. In addition, the expressions of PI3K and AKT showed an up-regulation. In conclusion, miR-34c-5p was down-regulated in BAS and may inhibit fibroblast proliferation differentiation and EMT in BAS via the MDMX/p53 signaling axis. These findings expand the understanding of the role of miR-34c-5p and will help develop new treatment strategies for BAS.

TREATMENT OF CONGENITAL LARYNGEAL CYSTS IN NEWBORNS.

Congenital laryngeal cysts are rare lesions that may occur in newborns, characterized by symptoms of respiratory obstruction and severe dyspnea. The aim of this study was to indicate optimal surgical treatment of congenital laryngeal cysts in newborns. We present a case series of five neonates treated for congenital laryngeal cysts during the 2011-2017 period at our pediatric tertiary care hospital. Patient age ranged from one day to 14 days. All patients had unilateral cysts. After surgical excision, burning of the walls of the cysts was performed by a CO2 laser. In one case, after four months, a recurrent cyst appeared, and re-operation was performed. Our relatively small case series indicates that symptoms such as stridor and labored breathing can occur already during the first days of life and potentially endanger the patient's life. Complete excision of the cyst and burning of its walls with CO2 laser leads to complete cure and prevent recurrence of the lesion.

Brachycephalic obstructive airway syndrome: much more than a surgical problem.

Brachycephalic obstructive airway syndrome (BOAS) is a chronic, lifelong, debilitating, primarily obstructive airway disease which adversely affects the quality of life of many popular dog breeds. Respiratory restriction in bulldog breeds, pugs and Boston terriers frequently co-exist with pathologies of the gastrointestinal tract. In addition, many brachycephalic dogs that appear clinically normal are, in fact suffering from chronic hypoxia and its systemic consequences. Concurrent gastroesophageal reflux-associated conditions, sleep disorders and systemic hypertension further impact the welfare of affected dogs. Acceptance of BOAS and associated clinical signs as being 'normal for the breed' is common amongst owners. While surgical correction of the upper airway is the mainstay of treatment, the provision of subsequent, frequently lifelong medical management is equally important for the maintenance of an acceptable quality of life, at least for some affected patients. Here we review the current knowledge concerning brachycephaly, combine it with shared clinical experience in the management of this debilitating condition, and discuss ethical considerations and the responsibility of veterinarians to contribute public education and to support appropriate breed standards for animals under our care.

[Assessment of clinical signs of brachycephalic obstructive airway syndrome and other breed-specific diseases in pug dogs - an online survey]. / Einschätzung von Symptomen des brachyzephalen obstruktiven Atemwegssyndroms und anderen rassetypischen Erkrankungen bei Mops-Hunden ­ eine Online-Umfrage.

OBJECTIVE: The aim of the study was to investigate the awareness for the breed-related brachycephalic obstructive airway syndrome (BOAS) and the occurrence of other breed-typical diseases within the framework of an online survey for pug owners. MATERIAL AND METHODS: A digital questionnaire for owners was created, distributed via social media and subsequently evaluated. RESULTS: The questionnaire was completed by 1220 pug owners. According to the owners, 32 % (344/1073) of the animals that did not undergo airway dilatation surgery show slight and 3 % (34/1073) show distinct breathing sounds when at rest. 86 % (326/378) of the owners perceive these breathing sounds as "normal, breed-specific" and 14 % (51/378) consider them as sign of "disease". 20 % (210/1073) of the animals are considered "somewhat" and 5 % (57/1073) "frequently tired and quickly short of breath" after a small amount of time. 24 % (245/1220) of all animals suffer from ocular diseases, 10 % (122/1220) from skin diseases and 11 % (134/1220) from spinal diseases, among others. CONCLUSION: The survey shows that with 67 % (814/1220) more than half of the pug owners perceive clinical signs of BOAS and/or other breed-specific diseases in their animals, however, a large proportion consider these as being non-problematic. CLINICAL RELEVANCE: The present study reveals that the animals' clinical limitations associated with brachycephaly are oftentimes not perceived as being pathologic and are hence underestimated by the owners.

VEGF receptor 2 (KDR) protects airways from mucus metaplasia through a Sox9-dependent pathway.

Mucus-secreting goblet cells are the dominant cell type in pulmonary diseases, e.g., asthma and cystic fibrosis (CF), leading to pathologic mucus metaplasia and airway obstruction. Cytokines including IL-13 are the major players in the transdifferentiation of club cells into goblet cells. Unexpectedly, we have uncovered a previously undescribed pathway promoting mucous metaplasia that involves VEGFa and its receptor KDR. Single-cell RNA sequencing analysis coupled with genetic mouse modeling demonstrates that loss of epithelial VEGFa, KDR, or MEK/ERK kinase promotes excessive club-to-goblet transdifferentiation during development and regeneration. Sox9 is required for goblet cell differentiation following Kdr inhibition in both mouse and human club cells. Significantly, airway mucous metaplasia in asthmatic and CF patients is also associated with reduced KDR signaling and increased SOX9 expression. Together, these findings reveal an unexpected role for VEGFa/KDR signaling in the defense against mucous metaplasia, offering a potential therapeutic target for this common airway pathology.

Assisting PNA transport through cystic fibrosis human airway epithelia with biodegradable hybrid lipid-polymer nanoparticles.

Cystic fibrosis (CF) is characterized by an airway obstruction caused by a thick mucus due to a malfunctioning Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. The sticky mucus restricts drugs in reaching target cells limiting the efficiency of treatments. The development of new approaches to enhance drug delivery to the lungs represents CF treatment's main challenge. In this work, we report the production and characterization of hybrid core-shell nanoparticles (hNPs) comprising a PLGA core and a dipalmitoylphosphatidylcholine (DPPC) shell engineered for inhalation. We loaded hNPs with a 7-mer peptide nucleic acid (PNA) previously considered for its ability to modulate the post-transcriptional regulation of the CFTR gene. We also investigated the in vitro release kinetics of hNPs and their efficacy in PNA delivery across the human epithelial airway barrier using an ex vivo model based on human primary nasal epithelial cells (HNEC) from CF patients. Confocal analyses and hNPs transport assay demonstrated the ability of hNPs to overcome the mucus barrier and release their PNA cargo within the cytoplasm, where it can exert its biological function.

Fine particulate matter induces airway inflammation by disturbing the balance between Th1/Th2 and regulation of GATA3 and Runx3 expression in BALB/c mice.

The present study aimed to examine the effects of 2.5 µm particulate matter (PM2.5) on airway inflammation and to investigate the possible underlying mechanism. Specifically, the focus was on the imbalance of T helper (Th)1/Th2 cells and the dysregulated expression of transcription factors, including trans­acting T cell­specific transcription factor 3 (GATA3), runt­related transcription factor 3 (Runx3) and T­box transcription factor TBX21 (T­bet). In this study, ambient PM2.5 was collected and analyzed, male BALB/c mice were sensitized and treated with PBS, ovalbumin (OVA), PM2.5 or OVA + PM2.5. The effects of PM2.5 alone or PM2.5 + OVA on immunopathological changes, the expression of transcription factors GATA3, Runx3 and T­bet, and the imbalance of Th1/Th2 were investigated. It was found that PM2.5 + OVA co­exposure significantly enhanced inflammatory cell infiltration, increased higher tracheal secretions in lung tissue and upregulated respiratory resistance response to acetylcholine compared with PM2.5 or OVA single exposure and control groups. In addition, higher protein and mRNA expression levels of Th2 inflammatory mediators interleukin (IL)­4, IL­5 and IL­13 in bronchoalveolar lavage fluid were observed in PM2.5 + OVA treated mice, whereas the expression levels of GATA3 and STAT6 were exhibited in mice exposed to OVA + PM2.5 compared with the OVA and PM2.5 groups. By contrast, PM2.5 exposure decreased the protein and mRNA expression levels of Th1 cytokine interferon­Î³ and transcription factors Runx3 and T­bet, especially among asthmatic mice, different from OVA group, PM2.5 exposure only failed to influence the expression of T­bet. To conclude, PM2.5 exposure evoked the allergic airway inflammation response, especially in the asthmatic mouse model and led to Th1/Th2 imbalance. These effects worked mainly by upregulating GATA3 and downregulating Runx3. These data suggested that Runx3 may play an important role in PM2.5­aggravated asthma in BALB/c mice.

Huge Tornwaldt Cyst With Otitis Media With Effusion.

Tornwaldt cyst is a relatively rare lesion that is found in the posterior wall of the nasopharynx. It occurs in the midline bursa of the nasopharynx and represents a persistent communication between the roof of the nasopharynx and the notochordal remnants. Smaller cysts are usually asymptomatic; cysts exceeding a diameter of 1 to 2 cm may be symptomatic. Magnetic resonance imaging is the best imaging modality for diagnosing Tornwaldt cyst. We present a rare case of a huge Tornwaldt cyst completely obstructing the nasopharyngeal airway.

Variable Mechanisms of Sudden and Unexpected Death in Cases of Occult Carcinoma of the Larynx.

ABSTRACT: Two cases of clinically undiagnosed laryngeal squamous cell carcinomas in men aged 57 and 66 years, respectively, are reported that resulted in sudden death from upper airway occlusion. The cause of the terminal event differed between the 2 cases with acute airway narrowing being precipitated by tenacious mucopurulent secretions in case 1 and hemorrhage from surface ulceration with glottic occlusion by blood clot in case 2. At autopsy, the immediate cause of acute airway compromise in cases of space-occupying laryngeal lesions may, therefore, be due to the synergistic effects of different factors.

The evolution of pulmonary function in childhood onset Mucopolysaccharidosis type I.

Respiratory outcomes in Mucopolysaccharidosis Type I (MPS I), have mainly focused on upper airway obstruction, with the evolution of the restrictive lung disease being poorly documented. We report the long-term pulmonary function outcomes and examine the potential factors affecting these in 2 cohorts of MPS I patients, those who have undergone Haematopoietic Stem Cell Transplantation (HSCT) and those treated with Enzyme Replacement Therapy (ERT). The results were stratified using the American Thoracic Society (ATS) guidelines. 66 patients, capable of adequately performing testing, were identified by a retrospective case note review, 46 transplanted (45 Hurler, 1 Non-Hurler) and 20 having ERT (17 Non-Hurler and 3 Hurler diagnosed too late for HSCT). 5 patients died; 4 in the ERT group including the 3 Hurler patients. Overall 14% of patients required respiratory support (non-invasive ventilation (NIV) or supplemental oxygen)) at the end of follow up. Median length of follow-up was 12.2 (range = 4.9-32) years post HSCT and 14.34 (range = 3.89-20.4) years on ERT. All patients had restrictive lung disease. Cobb angle and male sex were significantly associated with more severe outcomes in the HSCT cohort, with 49% having severe to very severe disease. In the 17 Non-Hurler ERT treated patients there was no variable predictive of severity of disease with 59% having severe to very severe disease. During the course of follow up 67% of the HSCT cohort had no change or improved pulmonary function as did 52% of the ERT patients. However, direct comparison between therapeutic modalities was not possible. This initial evidence would suggest that a degree of restrictive lung disease is present in all treated paediatrically diagnosed MPS I and is still a significant cause of morbidity, though further stratification incorporating diffusing capacity for carbon monoxide (DLCO) is needed.

Airway obstruction from tracheostomy balloon cuff herniation during oral cancer removal. Emergency successfully managed and lessons learnt from device malfunction.

OBJECTIVE: Tracheostomy tube cuff balloon herniation is a rare event and can determine airway obstruction. Sometimes the obstruction is not very evident but, if it is not correctly solved, can determine a severe hypoxia with patient's death. MATERIAL AND METHODS: We present a 49-year-old male patient, with cT4aN0M0 squamous cell carcinoma of the oral cavity, who was admitted to the hospital for definitive surgical resection. Due to mass an endo-oral intubation was not possible, so a surgical tracheotomy was performed. General anaesthesia was induced with Propofol (2 mg/kg) and Fentanil (1 mcg/kg) without gas. Surgery commenced via a trans-oral and trans-cervical approach, but it was halted after approximately 2 min as oximetry demonstrated a progressive fall from 98% to 78%. After confirmation of correct function of anaesthetic devices, the endotracheal cannula was tested; although surgeon deflated the tube cuff, repositioned the tube, and re-inflated the cuff, oxygen saturation did not change. So, the cannula was changed and patient's saturation increased up to normal value. RESULTS: The balloon cuff of the cannula showed a herniation, responsible of insufficient ventilation. CONCLUSIONS: Cuff herniation should be considered in case of unexpected airway obstruction, and a systematic, rapid approach to investigation and management should ensure timely identification and correction.

Histological and mechanical comparisons of arytenoid cartilage between 4 brachycephalic and 8 non-brachycephalic dogs: A pilot study.

Brachycephalic airway syndrome (BAS) is a well-established cause of respiratory distress in dogs. BAS without surgical correction results in eventual laryngeal collapse. Arytenoid lateralization has been used to treat severe laryngeal collapse with some highly variable results. Chondromalacia and decreased stiffness of the arytenoid cartilage has been postulated a source of failure after arytenoid lateralization but no report of the histological characteristics and mechanical strength of arytenoid cartilage in brachycephalic dogs has been reported. Here we report histological and mechanical features in arytenoid cartilage of brachycephalic dogs. We identified the arytenoid cartilage in brachycephalic dogs presented degenerative histological characteristics and decreased load to failure and stiffness compared to that in non-brachycephalic dogs. Together, these observations suggest that degenerative condition of arytenoid cartilage in brachycephalic dogs could contribute to chondromalacia and mechanical weakness of arytenoid cartilage and result in cause of failure after arytenoid lateralization.

Massive paediatric pulmonary haemorrhage in Dieulafoy's disease: Roles of CT angiography, embolisation and bronchoscopy.

Acute, major pulmonary haemorrhage in children, is rare, may be life-threatening and at times presents atypically. Dieulafoy's disease of the bronchus presenting with recurrent or massive hemoptysis was first described in adults. Prior to reviewing the literature, we report an illustrative case of bronchial Dieulafoy's disease (BDD) in a child presenting unusually with massive apparent hematemesis. The source of bleeding is a bronchial artery that fails to taper as it terminates within the bronchial submucosa. A high index of suspicion is required to identify such lesions via radiological imaging and the role of bronchial artery embolisation is highlighted with video images of angiography included.

Role of radiotherapy in the management of malignant airway obstruction.

BACKGROUND: A significant proportion of lung cancer patients suffer from malignant airway obstruction (MAO). Palliative external beam radiotherapy (EBRT) is often used to control the symptoms caused by MAO. In this study, we report the effect of palliative EBRT on lung cancer with MAO and analyze the factors that influence it. METHODS: This study included 75 patients with MAO in lung cancer who underwent palliative EBRT, between 2009 and 2018 and were analyzed retrospectively. Change of dyspnea, tumor response, and overall survival (OS) were recorded. Univariate and multivariate analyses were performed to determine the prognostic factors for treatment outcomes. RESULTS: The median follow-up duration was 2.5 months, and median OS was 2.3 months. Out of 75 patients, dyspnea was improved in 46 patients (61.3%), and tumor was partially decreased in 39 patients (52%). Symptoms improved in all tumor responding patients. The symptom improvement was significantly affected by radiation dose and time to EBRT. The tumor response was significantly affected by pathology, radiation dose, and time to EBRT. CONCLUSIONS: Palliative EBRT is an effective and safe treatment option for patients with MAO in lung cancer. In particular, high-dose irradiation and prompt treatment can improve treatment results. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: In MAO patients, tumor response is an important factor for resolving dyspnea and improving survival rate. In order to increase the tumor response, high-dose irradiation and prompt treatment after symptoms occur are necessary. WHAT THIS STUDY ADDS: Our study reported the effects of EBRT and prognostic factors in MAO patients. We emphasize that palliative EBRT is a relatively safe and effective treatment in MAO patients, which is a complement to previous studies.

[Hamartochondroma: An unusual cause of endobronchial obstruction in smoking patients]. / L'hamartochondrome : cause inhabituelle d'obstacle endobronchique chez des patients fumeurs.

Endobronchial hamartochondroma is a rare benign tumor which differs from the parenchymal form in its symptomatology and also by its treatment which should be as conservative as possible. The endobronchial location is exceptional. Here we present the cases of two patients with endobronchial hamartochondroma associated with clinical manifestation, chest pain and repeated pulmonary infections, respectively. The diagnosis was made after performing a CT-scan, a PET-SCAN and histological analysis. After discussion in a multidisciplinary staff meeting, conservative treatment was chosen in both cases.

Correlation between the clinical severity of laryngomalacia and endoscopic findings.

OBJECTIVE: To correlate the clinical severity of laryngomalacia (LM) with endoscopic findings, swallowing evaluations and polysomnography in a cohort of patients. Method: We conducted a retrospective analysis between 2017-2018 on a cohort of patients diagnosed with upper airway obstruction (UAO), stridor, noisy breathing or laryngomalacia. This study took place at the Pediatric Pulmonology Department, Riley Children's Hospital, Indianapolis, United States of America. RESULTS:   There were 157 patients with laryngomalacia included in the study. Patients with severe LM were significantly younger than those with mild LM (p=0.0214) and moderate LM (p=0.0220). Subjects with type I of LM were significantly older than type III (p=0.0051). When associations were tested between polysomnogram (PSG) variables and clinical severity, there were significant associations with age at PSG. The overall apnea-hypopnea index (AHI) in mild (p=0.0103) and moderate (p=0.0242) were significantly lower than the severe group. The rapid eye movement (REM) AHI was significantly lower in moderate cases than severe (p=0.0134). The end-tidal carbon dioxide (EtCO2) peak was significantly lower in mild cases than severe (p=0.0141). The total sleep time (TST) peripheral capillary oxygen saturation (SpO2) 90% occurs in both mild (p=0.0197) and moderate (p=0.0498) were significantly lower than the severe group. CONCLUSIONS: The severity of the clinical manifestations of LM did not correlate with the different endoscopic types in our study. The presence of cyanosis was associated with type III LM. Rapid eye movement AHI and EtCO2 in polysomnogram were remained significantly associated with clinical severity.

A 55-Year-Old Man With Cough and Hematochezia.

CASE PRESENTATION: A 55-year-old man presented to the ED with a 3-week history of worsening cough and shortness of breath. He had blood-tinged sputum, fever, night sweats, and a 2.7 kg weight loss within the same period. For the past few days, he had taken amoxicillin-clavulanate for presumed sinusitis. Despite this, his symptoms persisted, prompting him to seek further evaluation. His medical history was significant for ulcerative colitis and he had some bloody diarrhea for the past few weeks. Medications included aspirin, mesalamine, multivitamins, folic acid, and herbal supplements including gingko biloba, ginseng, and turmeric-ginger. He never smoked and drank alcohol occasionally. Family history was notable for stroke and myocardial infarction.

Acid exposure disrupts mucus secretion and impairs mucociliary transport in neonatal piglet airways.

Tenacious mucus produced by tracheal and bronchial submucosal glands is a defining feature of several airway diseases, including cystic fibrosis (CF). Airway acidification as a driving force of CF airway pathology has been controversial. Here we tested the hypothesis that transient airway acidification produces pathologic mucus and impairs mucociliary transport. We studied pigs challenged with intra-airway acid. Acid had a minimal effect on mucus properties under basal conditions. However, cholinergic stimulation in acid-challenged pigs revealed retention of mucin 5B (MUC5B) in the submucosal glands, decreased concentrations of MUC5B in the lung lavage fluid, and airway obstruction. To more closely mimic a CF-like environment, we also examined mucus secretion and transport following cholinergic stimulation under diminished bicarbonate and chloride transport conditions ex vivo. Under these conditions, airways from acid-challenged pigs displayed extensive mucus films and decreased mucociliary transport. Pretreatment with diminazene aceturate, a small molecule with ability to inhibit acid detection through blockade of the acid-sensing ion channel (ASIC) at the doses provided, did not prevent acid-induced pathologic mucus or transport defects but did mitigate airway obstruction. These findings suggest that transient airway acidification early in life has significant impacts on mucus secretion and transport properties. Furthermore, they highlight diminazene aceturate as an agent that might be beneficial in alleviating airway obstruction.