Airway Abnormalities Research Articles

Ataxia telangiectasia mutated is required for efficient proximal airway epithelial cell regeneration following influenza A virus infection.

Children and young adults with mutant forms of ataxia telangiectasia mutated (ATM), a kinase involved in DNA damage signaling and mitochondrial homeostasis, suffer from recurrent respiratory infections, immune deficiencies, and obstructive airways disease associated with disorganized airway epithelium. We previously showed in mice how Atm was required to mount a protective immune memory response to influenza A virus [IAV; Hong Kong/X31 (HKx31), H3N2]. Here, Atm wildtype (WT) and knockout (Atm-null) mice were used to investigate how Atm is required to regenerate the injured airway epithelium following IAV infection. When compared with WT mice, naive Atm-null mice had increased airway resistance and reduced lung compliance that worsened during infection before returning to naïve levels by 56 days postinfection (dpi). Although Atm-null lungs appeared pathologically normal before infection by histology, they developed an abnormal proximal airway epithelium after infection that contained E-cadherin+, Sox2+, and Cyp2f2+ cells lacking secretoglobin family 1 A member 1 (Scgb1a1) protein expression. Patchy and low expression of Scgb1a1 were eventually observed by 56 dpi. Genetic lineage tracing in HKx31-infected mice revealed club cells require Atm to rapidly and efficiently restore Scgb1a1 expression in proximal airways. Since Scgb1a1 is an immunomodulatory protein that protects the lung against a multitude of respiratory challenges, failure to efficiently restore its expression may contribute to the respiratory diseases seen in individuals with ataxia telangiectasia.

Impaired differentiation of small airway basal stem/progenitor cells in people living with HIV

With highly active anti-retroviral therapy (HAART), higher incidence of airway abnormalities is common in the HIV population consistent with the concept of accelerated lung “aging”. Our previous findings demonstrated that HIV induces human airway basal cells (BC) into destructive and inflammatory phenotypes. Since BC function as stem/progenitor cells of the small airway epithelium (SAE), responsible for self-renewal and differentiation of SAE, we hypothesized that BC from people living with HIV (PLWH) may have altered differentiation capacity that contribute to premature aging. The data demonstrates that BC from PLWH have impaired capacity to differentiate in vitro and senescent phenotypes including shortened telomeres, increased expression of β-galactosidase and cell cycle inhibitors, and mitochondrial dysfunction. In vitro studies demonstrated that BC senescence is partly due to adverse effects of HAART on BC. These findings provide an explanation for higher incidence of airway dysfunction and accelerated lung aging observed in PLWH.

Prevalence of Diabetes and Hypertension among Chronic Obstructive Pulmonary Diseases Patients at a Tertiary Care Centre

Background: Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases. HT and DM have been recognized to coexist with COPD. Several risk factors have been associated with HT and DM in people with COPD: Smoking, systemic inflammation, obesity and physical inactivity. Objective: To estimate Prevalence of diabetes and hypertension in Chronic Obstructive Pulmonary Diseases amongst study participants. Material and Method: The Cross-sectional study was conducted on 161 diagnosed COPD patients from August 2017 to December 2019 in Department of Respiratory Medicine Medical College and Tertiary Health Care Institute Nashik was included. Written informed consent was taken from all study participants and those who gave consent were enrolled in the present study. Result: Out of 161 COPD patients, prevalence of hypertension was 45.96% while prevalence of DM was 22.36%. The Highest prevalence of DM in Female (33.33%), HTN in Male (48%) and both DM and HTN in Female (8.33%), active smokers were mostly associated with DM and/or HTN. In stage IV (71), DM, HTN and both DM and HTN were recorded in maximum no. of cases, whereas in patients of Stage I - COPD least level were found. Increase association of DM and/or HTN increases with severity of obstruction. Conclusion: Prevalence of HTN was recorded more than DM. DM and HTN were found to be more prevalence in severe and very severe COPD patients. The COPD patients should be screened for DM and HTN at the time of diagnosis to prevent DM and/or HTN related complications in COPD patients.

Surgical management of complex neonatal airway abnormalities.

The neonatal airway is subject to a variety of developmental abnormalities with a wide range of complexity. Symptomatic pathologies present in a spectrum ranging from simple noisy breathing or poor feeding to frank respiratory distress. Diagnosis requires a high index of suspicion, characterization of noisy breathing, and identification of obstructive symptoms such as increased work of breathing, retractions, and difficulty feeding. Surgical management is directed by the pathology. The past several years have seen an expansion of surgical innovation as endoscopic and open techniques have evolved. We reviewed articles related to neonatal and infant airway diagnoses since 2020 with the goal of providing a current review and update of developing techniques. Specifically, we discuss some of the exciting trends in surgical management of vocal fold paralysis, laryngeal clefts, subglottic stenosis, tracheobronchomalacia as well as the role of ex utero intrapartum therapy (EXIT procedures). An underlying theme in evolving surgical management is the exciting advancements in technology, including 3-D printing, and expansion of minimally invasive endoscopic techniques. Though some of these developments are in the initial stages of utilization, they may be potential sources to transform surgical management in the future.

The interplay between diabetes mellitus and chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM) are common and chronic disorders. COPD is characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities and it is considered currently the fourth leading cause of death worldwide. DM is a systemic disease characterized by a chronic hyperglycemia associated with inflammation and oxidative stress. The relationship between the two conditions is not completely understood and conflicting results are reported in the literature. Many studies have investigated the mechanisms through with the respiratory disease is associated with an increased risk of metabolic condition or whether the incidence risk of COPD in individuals affected by DM is higher. The link between the two chronic conditions has relevant implications in the management of patients affected by the both of them. Respiratory patients should be screened for diabetes mellitus as a frequent comorbidity of lung disease since therapeutic options should be assessed about risk-to-benefit ratios associated with the indication for the steroid use. Furthermore, the role of hyperglycemia on pulmonary function (e.g. infection or inflammatory processes) should be evaluated in DM. Finally, in presence of both diseases potential treatment interactions should be considered. In this overview we explored the common aspects of both clinical chronic illnesses and investigated the interplay between the two conditions.

ORIGINAL ARTICLE: STUDY OF SLEEP PATTERNS IN PATIENTS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A SINGLE TERTIARY CARE CENTRE STUDY

Introduction: Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases. Sleep problems and sleepiness are common in COPD patients, partly due to symptoms but also because of the medications used to treat COPD. Method: This was a cross-sectional observational study conducted at CD Hospital of GMC Jammu for a period of one year from December 2020 to November 2021. 60 subjects were taken for sleep study by polysomnography with Alice 5 sleep system. Aim: To find out total sleep period and sleep efficiency and to find out correlation between spirometric & polysomnoghraphic variables. Result: Mean age of study sample is 60 years with standard deviation of 6.9 years. No significant difference observed in age and sex of study sample. Conclusion: 18 (30%) having hypertension as co-morbid condition. 31 (51.7%) samples were having smoking history, while 112 (20%) were reformed smokers. Excessive daytime sleepiness were present in 10 (16.7%) of study sample, Snoring was present in 9 (15%) of study sample.

Endoscopic coblation-assisted and partial arytenoidectomy for infants with idiopathic bilateral vocal cord paralysis.

To review our experience with endoscopic coblation-assisted and partial arytenoidectomy (ECPA) in treating idiopathic bilateral vocal cord paralysis (BVCP).A retrospective analysis of thirty-three infants (19 boys and 14 girls, aged 1–10 months) with idiopathic BVCP undergoing ECPA was performed. The therapeutic process and outcomes (surgical success, swallowing function, and voice) were reviewed. The follow-up period was >33 months.Among the thirty-three infants with idiopathic BVCP, surgery was successful in twenty-nine cases but failed in four cases. Twenty-one, nine, and three patients underwent right, left, and bilateral ECPA, with surgical success rates of 90.5%, 100.0%, and 33.3%, respectively. In addition, four and six cases were combined with subglottic stenosis (SGS) and laryngomalacia, respectively. The surgical success rates of BVCP alone and BVCP+ other airway abnormalities were 95.6% and 70.0%, respectively. During the follow-up, five infants had slight difficulty swallowing, 12 infants had partial or complete recovery movement of at least one vocal cord with satisfactory voice outcome, and five infants had early granuloma formation, which disappeared spontaneously.ECPA appears to be a promising alternative to tracheostomy and initial management in infants with idiopathic BVCP who are free of other airway abnormalities.

Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease

SummarySome patients hospitalized with acute COVID-19 suffer respiratory symptoms that persist for many months. We delineated the immune-proteomic landscape in the airways and peripheral blood of healthy controls and post-COVID-19 patients 3 to 6 months after hospital discharge. Post-COVID-19 patients showed abnormal airway (but not plasma) proteomes, with an elevated concentration of proteins associated with apoptosis, tissue repair, and epithelial injury versus healthy individuals. Increased numbers of cytotoxic lymphocytes were observed in individuals with greater airway dysfunction, while increased B cell numbers and altered monocyte subsets were associated with more widespread lung abnormalities. A one-year follow-up of some post-COVID-19 patients indicated that these abnormalities resolved over time. In summary, COVID-19 causes a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to the ongoing activation of cytotoxic T cells.

Non-cardiovascular findings on chest CT angiography in children with congenital heart disease: How important are they?

BackgroundThere are only a few publications about the non-cardiovascular findings in children with congenital heart diseases explored by chest CT angiography. The purpose of our study is to evaluate the prevalence of non-cardiovascular findings on chest CT angiographies in children with congenital heart disease and to raise awareness about their importance among the radiologists.MethodsWe retrospectively reviewed the 272 chest CT angiographies performed in our pediatric radiology department between January 2017 and march 2021 and extracted the data of the 180 patients positive for a congenital heart disease. Then from that pool, we sorted out the non-cardiovascular findings into significant and non-significant in regard of their relevance or not in the patient’s management.ResultsNon-cardiovascular lesions were found in 58% (105/180) of our patients, and 49% (88/180) of them presented at least one significant non-cardiac lesion. Lung and airways abnormalities were found in 41% (74/180) of the cases, representing the majority of the non-cardiovascular findings. Syndromic associations were found in 17% (28/180) of our patients, including 14 cases of heterotaxic syndrome.ConclusionNon-cardiovascular findings are common in children with congenital heart disease. Reporting these associated lesions is a requisite for an optimal therapeutic management of these children. Radiologists should never forget that a Chest CT angiography in children is first and foremost a chest CT.

Pulmonary Involvement in Microscopic Polyangiitis: Computed Tomography Findings in 55 Patients With Analysis of Risk Factors for Recurrence.

Background and objectivePulmonary involvement is seen in up to 30% of microscopic polyangiitis (MPA) patients. Pulmonary radiological findings for MPA have been scarcely reported to date. This study was conducted to evaluate computed tomography (CT) and clinical findings at the time of MPA diagnosis as predictors for systemic or lung recurrence.MethodsWe retrospectively reviewed the medical records and radiological data of 55 MPA patients with pulmonary involvement who were admitted to our hospital between April 2008 and December 2016.ResultsAside from pulmonary lesions, lesions were found in the kidneys (52.7%), skin (7.3 %), and peripheral nerves (3.6%). Biopsies were performed for 29.1% of the patients, with an overall diagnostic accuracy of 78.9%. Parenchymal opacities (74.5%, mainly ground-glass opacities and reticular shadowing) were more commonly seen than airway abnormalities were (40.0%, mainly bronchiectasis). Systemic recurrence in the first year after diagnosis was found in 10.9% of the patients, and it mainly involved the kidneys or lungs. A serum WBC count ≥ 10,900/μL was a risk factor for predicting systemic recurrence within the first year after diagnosis according to the Cox regression analysis (HR 11.1, 95%CI: 1.3-95.9, p=0.028). Lung recurrence within five years after the diagnosis was observed in 9.1% of the patients. The incidences of reticular shadowing and honeycombing in thoracic CT at diagnosis were significantly higher in recurrence-positive patients than in recurrence-negative patients, but these differences could not be used to predict lung recurrence.ConclusionsGround glass opacities, reticular shadowing, and bronchiectasis are prominent thoracic CT findings for MPA. There are no radiological patterns capable of predicting recurrence. However, a serum WBC count ≥ 10,900/μL at diagnosis might be a predictive factor for systemic recurrence within the year.

Paediatric anterior larynx: presentations, associations and a review of the literature.

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. Here, we 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. Tertiary paediatric centre. 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. Over a 5.5-year period, 58 children with AL (28 females, mean age 0.38years) were matched with 58 controls (mean age 0.42years). 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<.05). There were significantly more children with dysmorphism in the AL group (29 vs. 9, p<.05). The prevalence of AL was 4.9% (SE 0.0063). AL was detected in 4.9% of a sample of children who had undergone airway examination for aerodigestive symptoms. It is significantly associated with dysmorphism, and swallowing difficulties that warrant instrumental evaluation.

Distraction Breathing Exercise in Managing Inducible Laryngeal Obstruction in a Female Patient.

Inducible laryngeal obstruction (ILO) describes as inappropriate, episodic, reversible laryngeal closure during inspiration, occurring at the glottic and/or supraglottic level, in response to external triggers causing exertional breathing difficulties. We describe a case of a female patient with an underlying major depressive disorder who presented with sudden onset of stridor and tachypnoea, whereby the external trigger was psychogenic in origin. Bedside flexible nasopharyngolaryngoscopy (FNPLS) showed characteristic findings of paradoxical adduction of vocal cords during inspiration. Arterial blood gas analysis, routine blood tests, chest radiography, and computed tomography (CT) scan of brain, neck, and thorax excluded neurological or airway abnormality. Bedside distraction breathing exercise alleviated the stridor and tachypnoea. The patient was managed by supportive psychotherapy, speech therapy, and anti-reflux medication and was discharged well with resolution of her respiratory distress. We would like to highlight that meticulous history along with physical examinations are imperative especially amongst Otorhinolaryngologists as emergent airway management tracheostomy would have been unnecessary and cause more stress and burden to the patient as well as family members.

Prevalence of Airway Abnormality after Tracheotomy at a Tertiary Safety Net Children’s Hospital

Introduction: Over 4500 pediatric tracheotomies are performed an-nually in the United States. However, there is no consensus on the appropriate time for surveillance endoscopy. The St. Christopher’s Hospital for Children implemented the Trach Safe Initiative to improve airway safety in tracheotomy-dependent children. A major component of this initiative is surveillance endoscopy. The objectives of this study are to describe the prevalence of abnormal airway changes in trach dependent patients, to identify and describe the frequency of airway interventions, and to ultimately minimize morbidity in this population. Method: A report consisting of a list of patients meeting our inclusion criteria was generated using CPT codes for tracheotomy and direct bronchoscopy and laryngoscopy at SCHC. A retrospective chart review of patients under the age of 18 who has had a tracheotomy from 2010 to 2020 was conducted in order to describe airway abnormalities after tracheotomy quantitatively andqualitatively. Result: 55 patients met inclusion criteria and were included in our study. Our study found the overall rate of abnormal findings onen-doscopy after tracheotomy is 72.7 % (p &lt; 0.05). The average time from tracheotomy to the time of initial surveillance endoscopy at SCHC was 884 days (95%CI 684 -1084). The most common abnormal finding was granulation tissue (29.1%), followed by supra-stomal collapse (12.7%), and subglottic stenosis (12.7%). 58.2% of patients undergoing endoscopy had an intervention. The most common intervention during endoscopy was excision of granulation tissue (25.4%) and trach change (23.6%) followed by tracheoplasty/stomoplasty (7.2%). Conclusion:Our study found a high rate of airway abnormality on surveillance endoscopy with a significant percentage of our patients requiring airway intervention. Our findings necessitate a guideline for routine surveillance endoscopy for our tracheotomy patients and the development of a database tracking airway abnormalities of patients in order to prepare a safe airway plan.

Fattori di rischio per infezione grave da SARS-CoV-2 nei bambini: i dati in era prevaccinale di un anno di epidemia confermano che i bambini che si ammalano gravemente sono pochi e con comorbidità

Risk Factors for Severe SARS-CoV-2 Infection in Children: Data in the pre vaccinal era of one year of epidemic confirm that children who become seriously ill are few and comorbid The results of a population-based surveillance conducted in 250 pediatric acute-care U.S.A. hospitals, during March 2020–May 2021 are described. Rates and risk factors for severe COVID-19 among a group of 2,293 children primarily admitted for COVID-19 are defined. Approximately 30% of the hospitalized children had severe COVID-19 and 0.5% died during hospitalization. By means of a multivariate analysis the possible risks of severe COVID-19 were identified. Among children aged &lt;2 years, chronic lung disease, neurologic disorders, cardiovascular disease, prematurity and airway abnormality were associated with severe COVID-19. Among children aged 2‒17 years, feeding tube dependence, diabetes mellitus and obesity were associated with severe COVID-19. These results are considered useful to identify children at risk of severe disease and who can benefit from COVID-19 prevention strategies, including vaccination.

Advances in the Study of Upper Airway Characteristics in Children with Malocclusion

Malocclusion is the malformation of teeth, jaw and skull caused by congenital genetic factors or acquired environmental factors in the process of children's growth and development, such as diseases, bad oral habits, abnormal substitute teeth, such as irregular arrangement of teeth, abnormal relationship between upper and lower dental arch, abnormal jaw size and shape, etc. Malocclusion is also accompanied by respiratory diseases and dysfunction, such as obstructive sleep apnea (OSA). Conversely, abnormal occlusion also leads to respiratory tract developmental disorders and dysfunction. The cranio-maxillofacial morphology is closely related to the upper airway morphology. They are cause and effect each other. In recent years, it has been found that orthodontic treatment can not only improve the malocclusion, but also has a significant effect on the upper airway volume. The abnormal upper airway in childhood will affect children's breathing, cause children's sleep apnea, and affect children's growth and development. At the same time, with the development of society, we pay more attention to children's face. Therefore, at present, the upper airway morphological characteristics, influencing factors and correction methods of malocclusion have become the focus of research.

Differentiating tracheobronchial involvement in granulomatosis with polyangiitis and relapsing polychondritis on chest CT: a cohort study

BackgroundIn patients with tracheobronchial involvement, the differential diagnosis between granulomatosis with polyangiitis (GPA) and relapsing polychondritis (RP) can be challenging. The aim of this study was to describe the characteristics of airway abnormalities on chest computed tomography (CT) in patients with GPA or RP and to determine whether specific imaging criteria could be used to differentiate them.MethodsGPA and RP patients with tracheobronchial involvement referred to a national referral center from 2008 to 2020 were evaluated. Their chest CT images were reviewed by two radiologists who were blinded to the final diagnosis in order to analyze the characteristics of airway involvement. The association between imaging features and a diagnosis of GPA rather than RP was analyzed using a generalized linear regression model.ResultsChest CTs from 26 GPA and 19 RP patients were analyzed. Involvement of the subglottic trachea (odds ratio for GPA=28.56 [95% CI: 3.17; 847.63]; P=0.001) and extensive airway involvement (odds ratio for GPA=0.02 [95% CI: 0.00; 0.43]; P=0.008) were the two independent CT features that differentiated GPA from RP in multivariate analysis. Tracheal thickening sparing the posterior membrane was significantly associated to RP (odds ratio for GPA=0.09 [95% CI: 0.02; 0.39]; P=0.003) but only in the univariate analysis and suffered from only moderate interobserver agreement (kappa=0.55). Tracheal calcifications were also associated with RP only in the univariate analysis (odds ratio for GPA=0.21 [95% CI: 0.05; 0.78]; P=0.045).ConclusionThe presence of subglottic involvement and diffuse airway involvement are the two most relevant criteria in differentiating between GPA and RP on chest CT. Although generally considered to be a highly suggestive sign of RP, posterior tracheal membrane sparing is a nonspecific and an overly subjective sign.

Airway inflammation and dysbiosis in antibody deficiency despite the presence of IgG

Patients with antibody deficiency suffer chronic respiratory symptoms, recurrent exacerbations, and progressive airways disease despite systemic replacement of IgG. Little is known about the respiratory tract biology of these patients. We sought to measure immunoglobulin levels, inflammatory cytokines, and mediators of tissue damage in serum and sputum from patients with antibody deficiency and healthy controls; to analyze the respiratory microbiome in the same cohorts. We obtained paired sputum and serum samples from 31 immunocompetent subjects and 67 antibody-deficient patients, the latter divided on computed tomography scan appearance into "abnormal airways" (bronchiectasis or airway thickening) or "normal airways." We measured inflammatory cytokines, immunoglobulin levels, neutrophil elastase, matrix-metalloproteinase-9, urea, albumin, and total protein levels using standard assays. We used V3-V4 region 16S sequencing for microbiome analysis. Immunodeficient patients had markedly reduced IgA in sputum but higher concentrations of IgG compared with healthy controls. Inflammatory cytokines and tissue damage markers were higher in immunodeficient patients, who also exhibited dysbiosis with overrepresentation of pathogenic taxa and significantly reduced alpha diversity compared with immunocompetent individuals. These differences were seen regardless of airway morphology. Sputum matrix-metalloproteinase-9 and elastase correlated inversely with alpha diversity in the antibody-deficient group, as did sputum IgG, which correlated positively with several inflammatory markers, even after correction for albumin levels. Patients with antibody deficiency, even with normal lung imaging, exhibit inflammation and dysbiosis in their airways despite higher levels of IgG compared with healthy controls.

Risk Factors for Severe COVID-19 in Children.

Describe population-based rates and risk factors for severe coronavirus disease 2019 (COVID-19) (ie, ICU admission, invasive mechanical ventilation, or death) among hospitalized children. During March 2020 to May 2021, the COVID-19-Associated Hospitalization Surveillance Network identified 3106 children hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection in 14 states. Among 2293 children primarily admitted for COVID-19, multivariable generalized estimating equations generated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) of the associations between demographic and medical characteristics abstracted from medical records and severe COVID-19. We calculated age-adjusted cumulative population-based rates of severe COVID-19 among all children. Approximately 30% of hospitalized children had severe COVID-19; 0.5% died during hospitalization. Among hospitalized children aged <2 years, chronic lung disease (aRR: 2.2; 95% CI: 1.1-4.3), neurologic disorders (aRR: 2.0; 95% CI: 1.5‒2.6), cardiovascular disease (aRR: 1.7; 95% CI: 1.2‒2.3), prematurity (aRR: 1.6; 95% CI: 1.1‒2.2), and airway abnormality (aRR: 1.6; 95% CI: 1.1‒2.2) were associated with severe COVID-19. Among hospitalized children aged 2 to 17 years, feeding tube dependence (aRR: 2.0; 95% CI: 1.5‒2.5), diabetes mellitus (aRR: 1.9; 95% CI: 1.6‒2.3) and obesity (aRR: 1.2; 95% CI: 1.0‒1.4) were associated with severe COVID-19. Severe COVID-19 occurred among 12.0 per 100 000 children overall and was highest among infants, Hispanic children, and non-Hispanic Black children. Results identify children at potentially higher risk of severe COVID-19 who may benefit from prevention efforts, including vaccination. Rates establish a baseline for monitoring changes in pediatric illness severity after increased availability of COVID-19 vaccines and the emergence of new variants.

Characteristics of airway resistance in obstructive sleep apnea patients with asthma on oscillometry

Background: Asthma and obstructive sleep apnea (OSA) are prevalent chronic respiratory disorders with a high tendency to coexist. Both diseases involve increased airway resistance in the upright position because of narrow upper or lower airways. Moreover, there is a marked increase in airway resistance in the supine position in patients with OSA. We verified the characteristics of OSA in combination with asthma. Methods: Airway resistance was measured by oscillometry in the upright and supine position in 11 healthy participants (control), 59 patients with OSA alone, and 33 OSA patients with asthma (coexistence) in the hospital between April 2014 and July 2020. We compared the differences in airway resistance between the upright and supine positions among the three groups. In addition, we performed cephalometry to evaluate the upper airway structure in patients with OSA alone and in patients with both OSA and asthma. Results: A marked increase in airway resistance due to postural change was observed in the “OSA alone” group compared to that in the control group. However, this was not observed in the “coexistence” and control groups. Moreover, the “coexistence” group had fewer structural abnormalities in the upper airway than the “OSA alone” group on cephalometry. Conclusions: The airway resistance of patients with OSA alone markedly increased with posture change because of upper airway abnormalities. However, there was a smaller increase with postural changes in OSA patients with asthma, suggesting the possibility of a smaller degree of upper airway abnormality compared to patients with OSA alone. Clinical Trial Registration number: This study is approved by the research ethics committee of the Shinshu University School of Medicine (permission number: 4272)

Increased susceptibility of cystic fibrosis airway epithelial cells to ferroptosis

BackgroundDefective chloride transport in airway epithelial cells (AECs) and the associated lung disease are the main causes of morbidity and early mortality in cystic fibrosis (CF). Abnormal airway iron homeostasis and the presence of lipid peroxidation products, indicative of oxidative stress, are features of CF lung disease.ResultsHere, we report that CF AECs (IB3-1) are susceptible to ferroptosis, a type of cell death associated with iron accumulation and lipid peroxidation. Compared to isogenic CFTR corrected cells (C38), the IB3-1 cells showed increased susceptibility to cell death upon exposure to iron in the form of ferric ammonium citrate (FAC) and the ferroptosis inducer, erastin. This phenotype was accompanied by accumulation of intracellular ferrous iron and lipid peroxides and the extracellular release of malondialdehyde, all indicative of redox stress, and increased levels of lactate dehydrogenase in the culture supernatant, indicating enhanced cell injury. The ferric iron chelator deferoxamine (DFO) and the lipophilic antioxidant ferrostatin-1 inhibited FAC and erastin induced ferroptosis in IB3-1 cells. Glutathione peroxidase 4 (GPX4) expression was decreased in IB3-1 cells treated with FAC and erastin, but was unchanged in C38 AECs. Necroptosis appeared to be involved in the enhanced susceptibility of IB3-1 AECs to ferroptosis, as evidenced by partial cell death rescue with necroptosis inhibitors and enhanced mixed lineage kinase domain-like (MLKL) localisation to the plasma membrane.ConclusionThese studies suggest that the increased susceptibility of CF AECs to ferroptosis is linked to abnormal intracellular ferrous iron accumulation and reduced antioxidant defences. In addition, the process of ferroptotic cell death in CF AECs does not appear to be a single entity and for the first time we describe necroptosis as a potential contributory factor. Iron chelation and antioxidant treatments may be promising therapeutic interventions in cystic fibrosis.Graphical