Airway Responsiveness Research Articles

Mechanism differences in the start time of sublingual immunotherapy in a mouse allergic airway inflammation model

Sublingual immunotherapy (SLIT) has received considerable attention as a method for allergen immunotherapy (AIT). However, the mechanism of SLIT, especially its timing, has not been thoroughly investigated. We evaluated therapeutic and prophylactic SLIT in an allergic airway inflammation model and evaluated their efficacies. Mice were intranasally exposed to Dermatophagoides farinae (Der f) extract and received SLIT before (prophylactic model) and after (therapeutic model) intranasal exposure of Der f. We investigated airway responsiveness, airway inflammation, allergen-specific antibodies, lung histology and single-cell RNA sequencing (scRNA-seq) and T-cell receptor sequencing were also investigated. SLIT in the therapeutic model was effective; however, the effects of SLIT in the prophylactic model were stronger and immune tolerance was maintained for three months. ScRNA-seq of lung CD4+CD25+ T cells revealed that the expansion of induced T regulatory (iTreg) cells was greater in the prophylactic model than that in the therapeutic model. Additionally, the TCR repertoire of iTregs from the prophylactic model was abundant, sharing many clones with the TCR repertoire of effector T cells. These data suggest that the prophylactic model of AIT is extremely effective and persistent, and may respond to allergen diversity, and provide evidence for the clinical recommendation of preventive AIT.

Cracking the Code of the Jugular Vagal Sensory Neurons in Allergic Airway Responsiveness

Cracking the Code of the Jugular Vagal Sensory Neurons in Allergic Airway Responsiveness

An item bank to measure health-related quality of life among young children (0-5-years-old) affected by respiratory illnesses – expert stakeholders and end-users from the Western Cape, South Africa

BackgroundHealth-related quality of life (HRQoL) is a crucial patient-centred outcome for developing policy. However, there is a lack of appropriate HRQoL measures for young children (0-5-years), who are particularly vulnerable to respiratory illnesses like pulmonary tuberculosis (PTB) and other respiratory infections, especially in low- and middle-income countries (LMICs). We aimed to develop a disease-specific HRQoL item bank for young children with acute and chronic respiratory illnesses.MethodsAn exploratory sequential design with three phases was used to develop a HRQoL item bank. The content validity of the item bank was evaluated by local and international experts specialising in HRQoL and child health. The group included paediatric pulmonologists, researchers with expertise in respiratory illnesses, and experts in scale development. Cognitive interviews with 37 caregivers of children with TB, pneumonia, adenovirus respiratory infection, other lower respiratory tract infections, reactive airway disease, and protracted bronchitis in Cape Town, South Africa, and consultations with 22 stakeholders were conducted for final revisions. The item bank was progressively refined at each phase of the study.FindingsThe Delphi experts recommended dividing the item bank into two age groups (0-2-years and 3-5-years) and using a 5-point Likert scale. Overall, 41 items (42%) met the predetermined > 70% threshold for inclusion in the item bank. Cognitive interviews confirmed that the domains were relevant. Minor modifications were made to five items in cohort 1 (0-2-years) and seven in cohort 2 (3-5-years), with 8 items (13%) and 14 items (22%) excluded. Phase 3 consultations emphasised the importance of including all seven domains and expanding the items to cover early childhood development, play, social interactions, and care routines. The final item bank includes versions for both age groups and incorporates these refinements.ConclusionAn item bank was developed as a first step to develop a comprehensive disease-specific HRQoL tool for young children with respiratory illnesses in an LMIC. Input from caregivers and content experts was crucial in creating two HRQoL item banks tailored to the developmental differences between 0 and 2 and 3-5-year age groups. Their contributions ensured the tool effectively captures age-appropriate aspects of HRQoL. Future studies should focus on assessing the validity and reliability of these item banks.

High-Flow Nasal Aerosol Therapy; Regional Aerosol Deposition and Airway Responsiveness.

Introduction: In normal subjects, during tidal breathing, aerosols deposit by settling in small airways. With obstructive lung disease (OLD), collapse of airways during expiration causes turbulence and increased deposition in central airways. High-flow nasal cannula (HFNC) therapy, washing out dead space, may affect deposition mechanisms and drug delivery. This study compared aerosol deposition and airway responsiveness in OLD after traditional and HFNC nebulization therapy. Methods: Twelve subjects with moderate to severe OLD participated in a two-day study. Spirometry was measured pre- and post-aerosol inhalation. On Day 1 (D1) subjects tidally inhaled radiolabeled albuterol (99mTc DTPA) by mouth via AeroTech II, (Biodex. Shirley, NY). Day 2 (D2) inhalation was via HFNC using i-AIRE (InspiRx, Inc. Somerset, NJ). The HFNC system (60 L/m) was infused by syringe pump at 50 mL/h. D2 lung deposition was monitored in real time by gamma camera to match D1. Pre and post heart rate, O2 sat, and nasopharyngeal deposition (NP) were measured. Mechanistic contributions were modeled using multiple linear regression (MLR) of deposition rate (DR µg/m) as a function of breathing frequency, airway geometry (FEV1), and parenchymal integrity (DLCO). Results: Albuterol lung depositions were matched (p = 0.13) with D1 central/peripheral (sC/P) ratios 1.99 ± 0.98. Following HFNC, peripheral deposition increased (31% ± 33%, sC/P = 1.51 ± 0.43, p = 0.01). D2/D1% change FVC increased by 16.1 ± 16.7% (p = 0.003). NP deposition averaged 333% of lung. Heart rate and O2 sat were unaffected (p = 0.31, p = 0.63 respectively). DR analysis was markedly different between D1 (R2 = 0.82) and D2 (R2 = 0.12). Conclusion: In subjects with OLD, HFNC nebulization at 60 L/min was well tolerated and increased peripheral drug delivery. Spirometry significantly improved. Systemic effects were undetected indicating limited nasal absorption. MLR demonstrated that different mechanisms of deposition govern traditional vs HFNC aerosol delivery. Breath-enhanced nebulization via HFNC may provide controllable and effective aerosol therapy in OLD.

The pathophysiology of dysphagia post-lung transplant: A systematic review.

One major consequence of lung transplantation is the development of oropharyngeal dysphagia. This systematic review aims to appraise and synthesize the available evidence of the use of instrumental assessments to outline the characteristics of post-lung transplant dysphagia. Following the identification of appropriate search terms for the question, a literature search was conducted in PubMed, Scopus, and the Health and Medical Collection of Proquest Research Library and included records between inception and September 14, 2023. Search strategies included the use of text words and subject headings (e.g., MeSH and Index terms) related to (1) dysphagia or swallowing (swallow*, deglutition disorder*), (2) lung transplant (lung transplant*, post-operative, post-lung), and (3) complications (adverse effects, *complications, treatment outcome). The literature search strategy yielded a total of 883 studies from the electronic database search, with no additional records identified through other sources. After the removal of duplicates (n = 96), a total of 787 studies were screened through title and abstracts which eliminated 775 studies. Six studies were ultimately included in the systematic review. The selected articles included patients who underwent lung transplantation and all but one study utilized a retrospective design. A lack of transparency regarding instrumental evaluation protocols (videofluoroscopic [VFSS] and Flexible Endoscopic Evaluation of Swallowing [FEES]) including the number and bolus types used during the instrumental evaluations appeared as a theme in the studies included. The Penetration-Aspiration Scale (PAS) was systematically utilized to measure dysphagia safety outcome. Handling of the PAS scale was not consistent across studies, however penetration or aspiration ranged from 52.4% up to 100%. Additionally, silent aspiration rates ranged from 14.2% to 61.9%. This review sought to describe the post-operative swallowing function and its physiological parameters following lung transplantation. We examined the results reported and the methods utilized in obtaining these results in the existing literature. Limited reporting practices for physiological parameters were found, however the airway invasion was reported in all studies with variation in degrees of swallowing safety related deficits, with PAS being the most widely used scale to describe airway invasion depth and response. Future studies exploring dysphagia outcomes post-lung transplant should comment on the altered physiological mechanisms of the swallow to further expand on the physiological deficits observed following transplantation in this group and allow for treatment planning. Level 1.

Comparison of the ED50 of Ciprofol Combined With or Without Fentanyl for Laryngeal Mask Airway Insertion in Children: A Prospective, Randomized, Open-Label, Dose-Response Trial.

This study aimed to estimate the effect of different doses of fentanyl on the median effective dose (ED50) of ciprofol for attenuating the airway and motor response to laryngeal mask airway (LMA) insertion response in healthy children. 90healthy preschool patients undergoing inguinal hernia repair surgery were randomly assigned to one of three groups: C0 (ciprofol+saline), C1 (ciprofol + fentanyl 1µg/kg), C2 (ciprofol + fentanyl 2µg/kg). Anesthesia was induced with either prepared fentanyl or saline, followed by ciprofol. The dose of ciprofol for each patient was determined using the up-and-down sequential study design. The primary outcome was the ED50 of ciprofol required for smooth LMA insertion in the three groups. Additionally, the time to loss of consciousness and any perioperative adverse events were recorded. Compared with the C0 group, the ED50 (95% confidence interval) of ciprofol in the C1 and C2 groups were significantly lower (1.81 [1.73-1.90]mg/kg versus 0.67 [0.64-0.71]mg/kg and 0.48 [0.42-0.54] mg/kg, respectively; P<0.05). Additionally, the ED50 of ciprofol in the C2 group was lower than that in the C1 group (0.42 [0.42-0.54] mg/kg vs 0.67 [0.64-0.71]mg/kg; P<0.05). Furthermore, the time to loss of consciousness in the C1 and C2 groups decreased by 60% and 53%, respectively, compared to the C0 group. There were no significant differences in the incidence of drug-related hypotension after anesthesia induction among the three groups. No adverse events of hypoxia, bradycardia, or injection pain were observed in any groups. In healthy, non-obese Chinese children undergoing elective inguinal hernia repair surgery, fentanyl 1µg/kg and 2µg/kg before ciprofol injection significantly reduced the ED50 of ciprofol for attenuating LMA response, with minimal occurrence of severe side effects.

The development and benefits of a pediatric airway response team in a children's hospital

The development and benefits of a pediatric airway response team in a children's hospital

Prescription Pattern of Beta Blockers in Patients Diagnosed with Heart Failure

This study will be helpful to detect the dosage, frequency and duration of beta blockers which is prescribed for heart failure patients that is followed the guideline. The goal of the study was to describe the prescription pattern of beta blockers in patients diagnosed with heart failure. Hypothyroidism, hypertension, type 2 diabetes mellitus patients are very prone to get Heart failure. Beta blockers should be prescribed, respective with the symptoms that occurred specifically to a particular patient. This study helped to detect the parameters of prescribing beta blockers in different symptoms and co morbidities. A Total of 39 patients, among them It was observed that (46.05%) patients having heart failure were from age group 48-57, followed by (2.5%) of 78-87 age group, of which the males (58.96%) proportion where seems more than the females (41.04%). The prescription pattern for heart failure patients were found as 100% Beta adrenergic blockers, such as metoprolol-65%, bisoprolol-22%, Carvedilol-15% were given. It is evident that the beta blockers are mainly prescribed according to the symptoms, carvedilol exhibits a more pronounced BP lowering effect as a consequence of its α1- receptor blocking activities and thus causes more frequent dizziness and hypotension. In patients predisposed to symptomatic hypotension, metoprolol succinate may be the more desirable whereas in patients with uncontrolled hypertension, carvedilol may be preferred. A selective β1-blocker such as metoprolol succinate is a reasonable option for patients with reactive airway disease.

Intravenous Bacillus Calmette-Guérin (BCG) Induces a More Potent Airway and Lung Immune Response than Intradermal BCG in Simian Immunodeficiency Virus-infected Macaques.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the leading causes of death due to an infectious agent. Coinfection with HIV exacerbates M. tuberculosis infection outcomes in people living with HIV. Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, is effective in infants, but its efficacy in adolescents and adults is limited. In this study, we investigated the immune responses elicited by BCG administered via i.v. or intradermal (i.d.) routes in SIV-infected Mauritian cynomolgus macaques (MCM) without the confounding effects of M. tuberculosis challenge. We assessed the impact of vaccination on T cell responses in the airway, blood, and tissues (lung, thoracic lymph nodes, and spleen), as well as the expression of cytokines, cytotoxic effectors, and key transcription factors. Our results showed that i.v. BCG induces a robust and sustained immune response, including tissue-resident memory T cells in lungs, polyfunctional CD4+ and CD8αβ+ T cells expressing multiple cytokines, and CD8αβ+ T cells and NK cells expressing cytotoxic effectors in airways. We also detected higher levels of mycobacteria-specific IgG and IgM in the airways of i.v. BCG-vaccinated MCM. Although i.v. BCG vaccination resulted in an influx of tissue-resident memory T cells in lungs of MCM with controlled SIV replication, MCM with high plasma SIV RNA (>105 copies/ml) typically displayed reduced T cell responses, suggesting that uncontrolled SIV or HIV replication would have a detrimental effect on i.v. BCG-induced protection against M. tuberculosis.

COMPARISON OF TOPICAL AND INTRAVENOUS LIGNOCAINE IN PATIENTS UNDERGOING LARYNGEAL MASK AIRWAY INSERTION UNDER PROPOFOL: A RANDOMIZED CONTROLLED TRIAL

Laryngeal mask airway (LMA) insertion is a common technique used in general anesthesia, but it may induce airway reflexes such as coughing, gagging, and laryngospasm. Lignocaine, whether administered topically or intravenously, is often used to suppress these reflexes. However, the comparative efficacy of these two routes remains unclear. Objective: This study aims to compare the effectiveness of topical versus intravenous lignocaine in facilitating LMA insertion and minimizing airway complications in patients undergoing propofol anesthesia. Methods: A randomized controlled trial was conducted on 62 patients undergoing elective surgeries under general anesthesia at a tertiary care hospital. Patients were randomly assigned into two groups: Group A (n = 31) received 40 mg of topical lignocaine aerosol, while Group B (n = 31) received intravenous lignocaine 1.5 mg/kg. Both groups were induced with propofol (2 mg/kg) prior to LMA insertion. Primary outcomes included the number of LMA insertion attempts, airway responses (coughing, gagging, laryngospasm), and hemodynamic parameters (systolic blood pressure, diastolic blood pressure, and heart rate) recorded at baseline and 1, 2, and 3 minutes post-insertion. Results: LMA insertion on the first attempt was successful in 93.5% of patients in the topical lignocaine group compared to 74.2% in the intravenous group (p = 0.03). Airway reflexes were significantly lower in the topical group, with coughing, gagging, and laryngospasm rates of 6.5%, 16.1%, and 9.7%, respectively, compared to 32.3%, 45.2%, and 29.0% in the intravenous group (p &lt; 0.05). Hemodynamic parameters, including systolic and diastolic blood pressure and heart rate, showed no significant differences between the two groups at baseline or post-insertion. Conclusion: Topical lignocaine significantly improves conditions for LMA insertion compared to intravenous lignocaine, resulting in fewer airway complications while maintaining similar hemodynamic stability. Therefore, topical lignocaine is recommended for optimizing LMA insertion during propofol anesthesia.

Pulmonary Administration of TLR2/6 Agonist after Allergic Sensitization Inhibits Airway Hyper-Responsiveness and Recruits Natural Killer Cells in Lung Parenchyma.

Asthma is a chronic lung disease with persistent airway inflammation, bronchial hyper-reactivity, mucus overproduction, and airway remodeling. Antagonizing T2 responses by triggering the immune system with microbial components such as Toll-like receptors (TLRs) has been suggested as a therapeutic concept for allergic asthma. The aim of this study was to evaluate the effect of a TLR2/6 agonist, FSL-1 (Pam2CGDPKHPKSF), administered by intranasal instillation after an allergic airway reaction was established in the ovalbumin (OVA) mouse model and to analyze the role of natural killer (NK) cells in this effect. We showed that FSL-1 decreased established OVA-induced airway hyper-responsiveness and eosinophilic inflammation but did not reduce the T2 or T17 response. FSL-1 increased the recruitment and activation of NK cells in the lung parenchyma and modified the repartition of NK cell subsets in lung compartments. Finally, the transfer or depletion of NK cells did not modify airway hyper-responsiveness and eosinophilia after OVA and/or FSL-1 treatment. Thus, the administration of FSL-1 reduces airway hyper-responsiveness and bronchoalveolar lavage eosinophilia. However, despite modifications of their functions following OVA sensitization, NK cells play no role in OVA-induced asthma and its inhibition by FSL-1. Therefore, the significance of NK cell functions and localization in the airways remains to be unraveled in asthma.

Stimulation of the internal superior laryngeal nerve as a potential therapy for obstructive sleep apnea in a porcine model.

Impaired pharyngeal sensing of negative pressure (NP) can lead to a blunted response of the upper airway dilator muscles and contribute to the development of obstructive sleep apnea (OSA). This response is modulated by the nerve fibers in the internal branch of the superior laryngeal nerve (iSLN), mediating negative pressure sensation. Artificial excitation of these fibers could be a potential treatment target for OSA. To evaluate this, electrostimulation of the iSLN was performed in a porcine-isolated upper airway model. Artificial obstructions were induced by varying the levels of negative pressure, and the ability of the animal to resolve these obstructions was evaluated. The pressure at which the animal was still able to resolve the obstruction was quantified as "Resolvable Pressure." Thereby, the effects on pharyngeal patency (n = 35) and the duration of the therapeutic effect outlasting the stimulation (n = 6) were quantified. Electrostimulation before the introduction of an artificial obstruction improved the median resolvable pressure from -28.3 cmH2O [IQR: -45.9; -26.1] to -92.6 cmH2O [IQR: -105.1; -78.6]. The median therapeutic effect was found to outlast the last stimulation burst applied by 163 s when five stimulation bursts were applied in short succession [IQR: 58; 231], 58 s when two were applied [IQR: 7; 65], and 6 s when one was applied [IQR: 0; 51]. Stimulation of the iSLN increased electromyography (EMG) in the genioglossus (GG). The proposed treatment concept can improve pharyngeal patency in the model. Transfer of the results to clinical application could enable the development of a new neuromodulation therapy for OSA.NEW & NOTEWORTHY Electrostimulation before the introduction of an artificial obstruction to induce artificial sleep apnea in the pig model improves the response of the upper airway to negative pressure (NP). The electrostimulation creates a sustained therapeutic effect that outlasts the initial electrostimulation. The use of this therapy in clinical practice has the potential to treat obstructive sleep apnea (OSA).

Release of ATP in the lung evoked by inhalation of irritant gases in rats.

Adenosine triphosphate (ATP) can be released into the extracellular milieu from various types of cells in response to a wide range of physical or chemical stresses. In the respiratory tract, extracellular ATP is recognized as an important signal molecule and trigger of airway inflammation. Chlorine (Cl2), sulfur dioxide (SO2), and ammonia (NH3) are potent irritant gases and common industrial air pollutants due to their widespread uses as chemical agents. This study was carried out to determine if acute inhalation challenges of these irritant gases, at the concentration and duration simulating the accidental exposures to these chemical gases in industrial operations, triggered the release of ATP in the rat respiratory tract; and if so, whether the level of ATP in bronchoalveolar lavage fluid (BALF) evoked by inhalation challenge of a given irritant gas was elevated by chronic allergic airway inflammation. Our results showed: 1) inhalation of these irritant gases caused significant increases in the ATP level in BALF, and the magnitude of evoked ATP release was in the order of Cl2 > SO2 > NH3. 2) Chronic airway inflammation induced by ovalbumin-sensitization markedly elevated the ATP level in BALF during baseline (breathing room air) but did not potentiate the release of ATP in the lung triggered by inhalation challenges of these irritant gases. These findings suggested a possible involvement of the ATP release in the lung in the regulation of overall airway responses to acute inhalation of irritant gases and the pathogenesis of chronic allergic airway inflammation.NEW & NOTEWORTHY Extracellular adenosine triphosphate (ATP) is a contributing factor and signaling molecule of airway inflammation. This study demonstrated for the first time that the ATP release in the lung was markedly elevated after acute inhalation challenges of three common industrial air pollutants; the order of the response magnitude was chlorine > sulfur dioxide > ammonia. These findings provided new information and improved our understanding of the adverse pulmonary effects caused by accidental inhalation exposures to these irritant gases.

Risk of Instrumental Delivery in Maternal Obesity: Estimates With Measures of Effect Size.

Background: Obesity, defined as a body mass index ≥30 kg/m2, is epidemic in the United States and is associated with increased risks of adverse events. Studies have examined the role of maternal obesity on the incidence of instrumental vaginal delivery, but the results are divided. However, these analyses used frequentist tests that risk false discovery. The purpose of this retrospective study was to quantify the association of maternal obesity to the need for instrumental delivery with measures of effect size. Measures of effect size allow assessment of the impact of clinical risk factors on outcomes of interest. Methods: All parturients aged ≥18 years in active labor at our facility from January 2018 to May 2019 were entered into this study. Patient demographics, previously reported comorbidities, and obstetric parameters were collected and analyzed to determine the clinical impact of maternal obesity on the incidence of instrumental delivery. One effect size measure, risk differences, was used to quantify the clinical effect of maternal obesity on the need for instrumental delivery. A generalized linear model was used to standardize the measures of effect size of previously reported comorbidities, including maternal obesity, and to determine their association with the need for instrumental delivery. Results: The incidences of chronic and gestational hypertension, preeclampsia, chronic diabetes, and reactive airway disease were higher in parturients with maternal obesity. Risk differences due to maternal obesity were observed in parturients presenting with shoulder dystocia but not in those who underwent oxytocin induction or in nulliparous parturients. Following regression analysis, maternal obesity did not clinically impact the need for instrumental delivery. Conclusion: These findings suggest that maternal obesity did not have a clinical impact on the need for instrumental delivery.

Airway epithelial cell response to RSV is mostly impaired in goblet and multiciliated cells in asthma

BackgroundIn patients with asthma, respiratory syncytial virus (RSV) infections can cause disease exacerbation by infecting the epithelial layer of the airways, inducing subsequent immune response. The type I interferon antiviral...

The Impact of High-Fructose Diet and Co-Sensitization to House Dust Mites and Ragweed Pollen on the Modulation of Airway Reactivity and Serum Biomarkers in Rats.

The topic of ragweed pollen (RW) versus house dust mites (HDMs) has often been deliberated, but the increasing incidence of co-sensitization between them has been scarcely addressed. Utilizing Sprague Dawley rats, we explored the effects of co-sensitization with the combination of HDMs and RW pollen extracts in correlation with high-fructose diet (HFrD) by in vitro tracheal reactivity analysis in isolated organ bath and biological explorations. Our findings unveiled interrelated connections between allergic asthma, dyslipidemia, and HFrD-induced obesity, shedding light on their compounding role through inflammation. The increased CRP values and airway hyperresponsiveness to the methacholine challenge suggest a synergistic effect of obesity on amplifying the existing inflammation induced by asthma. One of the major outcomes is that the co-sensitization to HDMs and RW pollen led to the development of a severe allergic asthma phenotype in rats, especially in those with HFrD. Therefore, the co-sensitization to these allergens as well as the HFrD may play a crucial role in the modulation of systemic inflammation, obesity, and airway reactivity.

Upper Airway and Translaryngeal Resistance During Mechanical Insufflation-Exsufflation

Mechanical insufflation-exsufflation (MI-E) uses positive and negative pressures to assist weak cough and help clear airway secretions. Laryngeal visualization during MI-E has revealed that inappropriate upper airway responses can impede its efficacy. However, the dynamics of pressure transmission in the upper airways during MI-E is unclear, as are the relationships between anatomical structure, pressure and airflow. Can airflow resistance through the upper airway and the larynx feasibly be calculated during MI-E, and if so, how are the pressures transmitted to the trachea? Cross-sectional study of ten healthy adults, where MI-E was provided with and without active cough, employing pressure settings +20/-40 and ±40 cmH2O. Airflow and pressure at the level of the facemask were measured using a pneumotachograph, while pressure transducers (positioned via transnasal fiberoptic laryngoscopy) recorded pressures above the larynx and within the trachea. Upper airway resistance (Ruaw) and translaryngeal resistance (Rtl) were calculated (cmH2O/L/sec) and compared to direct observations via laryngoscopy. Positive pressures reached the trachea effectively, while negative tracheal pressures during exsufflation were approximately half of the intended settings. Insufflation pressure increased slightly when passing through the larynx. Participant effort influenced tracheal pressures and the resistances, with findings consistent with laryngoscopic observations. During MI-E, resistance appears dynamic, with Ruaw exceeding Rtl. Inappropriate laryngeal closure increased Rtl during both positive and negative pressures. Upper airway and translaryngeal resistance can feasibly be calculated during MI-E. The findings indicate different transmission dynamics for positive and negative pressures, and that resistances are influenced by participant effort. The findings support using lower insufflation pressures and higher negative pressures in clinical practice.

RESPIRATORY DISEASES IN CHILDREN- ORAL FINDINGS AND DENTAL TREATMENT APPROACHES

Respiratory disease/condition is a medical term that encompasses pathological conditions affecting the organs and tissues that make gas exchange possible in the body. The most common respiratory disease which a pediatric dentist generally seen in practice is bronchial asthma ,cystic fibrosis,tuberculosis etc.Dental work occur close to the airways, and dental environments processes and setup also contribute to respiratory diseases.The management on the dental chair for this patient is different from the normal patient.Asthma affects about 1 in 10 children.The condition is characterized by acute respiratory distress and treated with medications aimed to reduce reaction to stimulants by the airway.Dental management involves attention to the status of the patient and awareness of stimulants of the reactive airway. Cystic fibrosis is an autosomal recessive disorder that effects epithelial cells of the respiratory,gastrointestinal and reproductive tracts leading to abnormal exocrine gland secretion.Management includes treatment of bronchial inflammation and infection. At Dental operatory patient should be treated under regulated temperature and others precaution .In this article ,common oral findings related to respiratory diseases will be discussed and the precautions and treatment approaches of dentist will be mentioned.

Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the SARS-CoV-2 spike protein

SARS-CoV-2-contributes to sickness and death in COVID-19 patients partly by inducing a hyper-proinflammatory immune response in the host airway. This hyper-proinflammatory state involves activation of signaling by NFκB, and unexpectedly, ENaC, the epithelial sodium channel. Post-infection inflammation may also contribute to "Long COVID"/PASC. Enhanced signaling by NFκB and ENaC also marks the airway of patients suffering from cystic fibrosis, a life-limiting proinflammatory genetic disease due to inactivating mutations in the CFTR gene. We therefore hypothesized that inflammation in the COVID-19 airway might similarly be due to inhibition of CFTR signaling by SARS-CoV-2 spike protein, and therefore activation of both NFκB and ENaC signaling. We used western blot and electrophysiological techniques, and an organoid model of normal airway epithelia, differentiated on an air–liquid-interface (ALI). We found that CFTR protein expression and CFTR cAMP-activated chloride channel activity were lost when the model epithelium was exposed to SARS-CoV-2 spike proteins. As hypothesized, the absence of CFTR led to activation of both TNFα/NFκB signaling and α and γ ENaC. We had previously shown that the cardiac glycoside drugs digoxin, digitoxin and ouabain blocked interaction of spike protein and ACE2. Consistently, addition of 30 nM concentrations of the cardiac glycoside drugs, prevented loss of both CFTR protein and CFTR channel activity. ACE2 and CFTR were found to co-immunoprecipitate in both basal cells and differentiated epithelia. Thus spike-dependent CFTR loss might involve ACE2 as a bridge between Spike and CFTR. In addition, spike exposure to the epithelia resulted in failure of endosomal recycling to return CFTR to the plasma membrane. Thus, failure of CFTR recovery from endosomal recycling might be a mechanism for spike-dependent loss of CFTR. Finally, we found that authentic SARS-CoV-2 virus infection induced loss of CFTR protein, which was rescued by the cardiac glycoside drugs digitoxin and ouabain. Based on experiments with this organoid model of small airway epithelia, and comparisons with 16HBE14o- and other cell types expressing normal CFTR, we predict that inflammation in the COVID-19 airway may be mediated by inhibition of CFTR signaling by the SARS-CoV-2 spike protein, thus inducing a cystic fibrosis-like clinical phenotype. To our knowledge this is the first time COVID-19 airway inflammation has been experimentally traced in normal subjects to a contribution from SARS-CoV-2 spike-dependent inhibition of CFTR signaling.

Role of Myeloperoxidase, Oxidative Stress, and Inflammation in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a lung complication of premature births. The leading causes of BPD are oxidative stress (OS) from oxygen treatment, infection or inflammation, and mechanical ventilation. OS activates alveolar myeloid cells with subsequent myeloperoxidase (MPO)-mediated OS. Premature human neonates lack sufficient antioxidative capacity and are susceptible to OS. Unopposed OS elicits inflammation, endoplasmic reticulum (ER) stress, and cellular senescence, culminating in a BPD phenotype. Poor nutrition, patent ductus arteriosus, and infection further aggravate OS. BPD survivors frequently suffer from reactive airway disease, neurodevelopmental deficits, and inadequate exercise performance and are prone to developing early-onset chronic obstructive pulmonary disease. Rats and mice are commonly used to study BPD, as they are born at the saccular stage, comparable to human neonates at 22-36 weeks of gestation. The alveolar stage in rats and mice starts at the postnatal age of 5 days. Because of their well-established antioxidative capacities, a higher oxygen concentration (hyperoxia, HOX) is required to elicit OS lung damage in rats and mice. Neutrophil infiltration and ER stress occur shortly after HOX, while cellular senescence is seen later. Studies have shown that MPO plays a critical role in the process. A novel tripeptide, N-acetyl-lysyltyrosylcysteine amide (KYC), a reversible MPO inhibitor, attenuates BPD effectively. In contrast, the irreversible MPO inhibitor-AZD4831-failed to provide similar efficacy. Interestingly, KYC cannot offer its effectiveness without the existence of MPO. We review the mechanisms by which this anti-MPO agent attenuates BPD.