Hyperreactive Airway Disease Research Articles

Prevalence and Severity of COVID-19 among Pediatric Patients with Atopy: A Cross-sectional Study in Kerman, Southeast Iran.

The tragic COVID-19 pandemic affected many children worldwide. Among the factors that may influence the course of viral infections including COVID-19, it is still uncertain whether atopy has a protective or predisposing role. The study aims to address the knowledge gap by investigating the prevalence and severity of COVID-19 among atopic children in Kerman, in 2022. A descriptive-analytical cross-sectional study on children with a history of atopy was performed in Kerman Medical University. Demographic information, type of atopy (including allergic rhinitis, Hyper-Reactive Airway Disease (HRAD) or asthma, eczema, urticaria, anaphylaxis, and food allergy), history of COVID-19 infection, and disease severity were recorded. A total of 1007 children and adolescents, (boys: 56.4%, girls: 43.6%, age:5.61±2.64 years) were included in the study. History of COVID-19 infection was positive in 53.5%, with 75.9% of the cases exhibiting mild disease severity. The frequency of atopies was HRAD or asthma (67.2%), allergic rhinitis (42.6%), and food allergy (27.4%). The frequency of COVID-19 cases was significantly higher among patients with HRAD or asthma, whereas it was significantly lower among those with food allergies, anaphylaxis, and eczema. Among atopic individuals, COVID-19 severity was significantly lower in those with allergic rhinitis, while the opposite trend was observed among food-allergic individuals. This study sheds light on the relationship between atopy and COVID-19 among pediatric patients. It seems specific types of atopies may influence the risk and severity of COVID-19 infection differently. A better understanding of these associations can inform clinical management and preventive measures for vulnerable pediatric populations.

Stimulatory effect of methylglyoxal on capsaicin-sensitive lung vagal afferents in rats: role of TRPA1.

Methylglyoxal (MG), a reactive metabolic byproduct of glycolysis, is a causative of painful diabetic neuropathy. Patients with diabetes are associated with more frequent severe asthma exacerbation. Stimulation of capsaicin-sensitive lung vagal (CSLV) afferents may contribute to the pathogenesis of hyperreactive airway diseases such as asthma. However, the possibility of the stimulatory effect of MG on CSLV afferents and the underlying mechanisms remain unknown. Our results showed that intravenous injection of MG (25 mg/kg, MG25) in anesthetized, spontaneously breathing rats elicited pulmonary chemoreflexes characterized by apnea, bradycardia, and hypotension. The MG-induced apneic response was reproducible and dose dependent. MG25 no longer evoked these reflex responses after perineural capsaicin treatment of both cervical vagi to block C-fibers' conduction, suggesting that the reflexes were mediated through the stimulation of CSLV afferents. Pretreatment with HC030031 [an antagonist of transient receptor potential ankyrin subtype 1 protein (TRPA1)] or AP18 (another TRPA1 antagonist), but not their vehicle, markedly attenuated the apneic response induced by MG25. Consistently, electrophysiological results showed that pretreatment with HC030031 largely attenuated the intense discharge in CSLV afferents induced by injection of MG25 in open-chest and artificially ventilated rats. In isolated CSLV neurons, the perfusion of MG evoked an abrupt and pronounced increase in calcium transients in a concentration-dependent manner. This stimulatory effect on CSLV neurons was also abolished by HC030031 treatment but not by its vehicle. In conclusion, these results suggest that MG exerts a stimulatory effect on CSLV afferents, inducing pulmonary chemoreflexes, and such stimulation is mediated through the TRPA1 activation.NEW & NOTEWORTHY Methylglyoxal (MG) is implicated in the development of painful diabetic neuropathy. A retrospective cohort study revealed an increased incidence of asthma exacerbations in patients with diabetes. This study demonstrated that elevated circulating MG levels stimulate capsaicin-sensitive lung vagal afferents via activation of TRPA1, which in turn triggers respiratory reflexes. These findings provide new information for understanding the pathogenic mechanism of diabetes-associated hyperreactive airway diseases and potential therapy.

Bronchodilator-responsive bronchiolar obstruction in term neonates: a case series

BackgroundBronchiolar obstruction, which causes airway obstruction in hyperresponsive airways, often results from the contraction of the airway's smooth muscles, increased viscid mucous secretions, and mucosal oedema consequent upon a reduced cyclic 3,5-adenosine monophosphate (c-AMP). These processes respond to bronchodilators. The six cases presented to us, in Edward Francis Small Teaching Hospital (EFSTH), Banjul, The Gambia, in the newborn period with clinical features suggesting obstruction with airway reactivity with response to bronchodilator treatment are presented here. Our capacity-limited literature search did not show any such report in neonates. This report highlights the need for this condition to be sought in neonates, medically managed in resource-poor countries without resorting to high-cost equipment use, and for its possible future classification.Case presentationWe report six cases of Gambian neonates consisting of four males and two females ages 2–27 days who presented to us with histories of fast breathing of a few hours duration and expiratory respiratory distress. All were term babies with rhonchi and demonstrable prolonged expiration with terminal effort. They all had a diagnosis of hyperreactive airway disease with bronchiolar obstruction. Five cases were first-time wheezers, while one was a recurrence. All were eventually treated with bronchodilators and steroids with good results. The median duration for resolution of most symptoms with treatment was two days, with a range of 1–5 days.ConclusionClinically determined bronchiolar obstructions in term neonates can be relieved with bronchodilators and steroids, and this treatment modality, if employed where the pathological process can be established, can reduce the demand on scarce resources in resource-poor countries.

Hyper-IgE syndrome with recurrent infections — An autosomal dominant multisystem disorder

Hyper IgE syndrome (HIES) is a rare disorder characterized by eczema, recurrent infections of the skin and lungs, typically with Staphylococcus aureus, Candida albicans and certain viruses, and elevated levels of serum IgE. Other clinical manifestations include characteristic facies (prominent forehead, broad nasal bridge and facial asymmetry), chronic eczematous dermatitis, retained primary dentition, recurrent pathological fractures, hyper-extensibility and scoliosis. The respiratory system involvement in HIES has been reported with HRAD. Here we presented a case of HIES with rare associations of Hyperreactive airway disease.

Surgical repair of umbilical hernia in a patient with Churg–Strauss syndrome under regional anaesthesia

Churg–Strauss syndrome (CSS), also referred to as eosinophilic granulomatosis with polyangiitis, is characterised by asthma, peripheral and tissue eosinophilia, extravascular granuloma formation and vasculitis of multiple organ systems. Patients with CSS have higher risk for hyper-reactive airway disease. Administering general anaesthesia in such patients may be deleterious as it requires airway manipulation, use of muscle relaxants some of which are associated with release of histamine and use of anti-cholinesterases which can cause bradycardia, increased secretions and bronchial hyper-reactivity. We report a case of a 36-year-old male with known CSS presented with umbilical hernia for mesh repair which was managed with regional anaesthesia.

Low-dose hyperoxia primes airways for fibrosis in mice after influenza A infection.

It is well known that supplemental oxygen used to treat preterm infants in respiratory distress is associated with permanently disrupting lung development and the host response to influenza A virus (IAV). However, many infants who go home with normally functioning lungs are also at risk for hyperreactivity after a respiratory viral infection. We recently reported a new, low-dose hyperoxia mouse model (40% for 8 days; 40×8) that causes a transient change in lung function that resolves, rendering 40×8 adult animals functionally indistinguishable from room air controls. Here we report that when infected with IAV, 40×8 mice display an early transient activation of TGFβ signaling and later airway hyperreactivity associated with peribronchial inflammation (profibrotic macrophages) and fibrosis compared with infected room air controls, suggesting neonatal oxygen induced hidden molecular changes that prime the lung for hyperreactive airways disease. Although searching for potential activators of TGFβ signaling, we discovered that thrombospondin-1 (TSP-1) is elevated in naïve 40×8 mice compared with controls and localized to lung megakaryocytes and platelets before and during IAV infection. Elevated TSP-1 was also identified in human autopsy samples of former preterm infants with bronchopulmonary dysplasia. These findings reveal how low doses of oxygen that do not durably change lung function may prime it for hyperreactive airways disease by changing expression of genes, such as TSP-1, thus helping to explain why former preterm infants who have normal lung function are susceptible to airway obstruction and increased morbidity after viral infection.

Environmental Exposures and Asthma in Active Duty Service Members.

Reports of respiratory symptoms, including asthma and hyper-reactive airway disease, have been more numerous in the media and medical literature since active duty service members (SM) began to support campaigns in South West Asia (SWA). Numerous environmental exposures have been reported and this review assesses the available evidence surrounding exposures, confounding conditions, and attempts to develop screening mechanisms. While particulate matter exposures and particularly exposure to burn pits have garnered much attention, a 2010 Armed Forces Health Surveillance Center report and 2011 Institute of Medicine publication did not identify a link between exposure to particulate matter with SM respiratory disease. The "Study of Active Duty Military for Pulmonary Disease related to Environmental Deployment Exposure," (STAMPEDE) and STAMPEDE II have not identified effective forms of routine screening and these and other sources point to the importance of other factors in SM respiratory disease. These include higher than anticipated rates of tobacco use in deployed settings, impacts of obesity, recurrence of childhood asthma, and of confounding conditions such as Paradoxical Vocal Fold Motion. As with the general population, a complex set of clinical inputs and environmental exposures surround asthma and similar respiratory processes in SM. Concrete relationships and mechanisms for assessment continue to be assessed and refined, but clear associations and pathways have remained elusive.

DOZ047.06: The MicroRNA levels in exhaled breath condensate of patients with esophageal atresia and tracheoesophageal fistula

Abstract Aim MicroRNAs (miRNAs) are noncoding RNAs that play a role in regulation of inflammation and cancer. It has been shown that miRNA-21 and 24 are downregulated in the exhaled breath condensate (EBC) of children with chronic inflammatory lung disease and asthma. A prospective study was performed to evaluate the miRNA-21 and 24 levels in the EBC of patients with esophageal atresia and tracheoesophageal fistula (EA-TEF). Methods Patients operated for EA-TEF were evaluated for age, sex, type of anomaly, surgical treatment, and respiratory problems. 500–1000 μl of EBC was obtained from all patients with Ecoscreen. miRNA-21 and 24 levels in EBC were analyzed with ELISA. The results of the study group were compared with a control group (CG) consisting of healthy children with no history of respiratory problems and allergy (n = 17). miRNA levels were compared with respiratory problems and gastroesophageal reflux (GER). Results Nineteen patients with EA-TEF with a mean age of 7.8 ± 3.2 years were enrolled in the study. The male–female ratio was 10:9. The mean age of the CG was 9.1 ± 3.6 years (P > 0.05). Distal fistula (78.9%) was the most common type of anomaly. 76.5% of cases required esophageal dilatations for strictures and 15.8% of them had fistula recurrence. Fifteen of the cases with EA were diagnosed as hyperreactive airway disease and require medical treatment. When miRNA levels were compared with CG (median = 0.68), EA cases had significantly decreased levels of miRNA-21 (median = 0.64, P < 0.05). There was no difference between groups for miRNA-24 levels (P > 0.05). The miRNA levels were also compared in patients with EA, according to positive pH testing for GER, use of proton pump inhibitor (PPI) treatment, and need for fundoplication. Patients with GER in pH test (median = 0.66) and fundoplication (median = 0.66) had increased levels of miRNA-21 than patients without reflux (median = 0.63) and surgical treatment (median = 0.64) (P < 0.05). The levels of miRNA-21 and 24 did not show any significant difference in patients with and without PPI treatment (P > 0.05). Conclusion The decreased levels of miRNA-21 in EBC suggest a hyperreactive airway problem in EA patients. Increased miRNA levels in EBC are associated with GER and its surgical treatment.

A clinical study of hyperreactive airway disease with wheeze in children aged five to twelve years with special reference to pulmonary function test

Background: Pulmonary function test is the easiest and most cost-effective method to evaluate respiratory functions. PFT can be measured by a simple instrument spirometer. Measuring PFT has been suggested as an important tool in understanding HRAD and its complications and management by all international guidelines. The objectives of this study were to clinically diagnose the hyperreactive airway disease in children coming to Navodaya Medical College, Raichur, of age group 5 to 12 years. And to perform pulmonary function test before and after the use of a bronchodilator.Methods: PFT was measured in 100 children who came with HRAD with wheeze using Spiro lab III spirometer. The child was given then nebulization with salbutamol and PFT was performed again after 30 min.Results: A total of 100 clinically diagnosed cases of HRAD of age group 5 to 12 years of both the gender was taken into the study, of which more than 44% of the children showed more than 20% improvement in parameters FEV1, PEF, FVC and marginal improvement in EV1/FVC post bronchodilator compared to their prebronchodilator parameters. The young children of both the gender showed better improvement than elder children.Conclusions: Spirometry is the best tool to assess HRAD even in younger children, early diagnosis and regular follow up with PFT helps to understand and prevent the progression of the disease with prompt treatment.

Estrogen Modulates the Sensitivity of Lung Vagal C Fibers in Female Rats Exposed to Intermittent Hypoxia.

Obstructive sleep apnea is mainly characterized by intermittent hypoxia (IH), which is associated with hyperreactive airway diseases and lung inflammation. Sensitization of lung vagal C fibers (LVCFs) induced by inflammatory mediators may play a central role in the pathogenesis of airway hypersensitivity. In females, estrogen interferes with inflammatory signaling pathways that may modulate airway hyperreactivity. In this study, we investigated the effects of IH on the reflex and afferent responses of LVCFs to chemical stimulants and lung inflammation in adult female rats, as well as the role of estrogen in these responses. Intact and ovariectomized (OVX) female rats were exposed to room air (RA) or IH for 14 consecutive days. On day 15, IH enhanced apneic responses to right atrial injection of chemical stimulants of LVCFs (e.g., capsaicin, phenylbiguanide, and α,β-methylene-ATP) in intact anesthetized females. Rats subjected to OVX prior to IH exposure exhibited an augmented apneic response to the same dose of stimulants compared with rats subjected to other treatments. Apneic responses to the stimulants were completely abrogated by bilateral vagotomy or perivagal capsaicin treatment, which blocked the neural conduction of LVCFs. Electrophysiological experiments revealed that in IH-exposed rats, OVX potentiated the excitability of LVCFs to stimulants. Moreover, LVCF hypersensitivity in rats subjected to OVX prior to IH exposure was accompanied by enhanced lung inflammation, which was reflected by elevated inflammatory cell infiltration in bronchoalveolar lavage fluid, lung lipid peroxidation, and protein expression of inflammatory cytokines. Supplementation with 17β-estradiol (E2) at a low concentration (30 μg/ml) but not at high concentrations (50 and 150 μg/ml) prevented the augmenting effects of OVX on LVCF sensitivity and lung inflammation caused by IH. These results suggest that ovarian hormones prevent the enhancement of LVCF sensitivity and lung inflammation by IH in female rats, which are related to the effect of low-dose estrogen.

Home environmental fungus: the hidden killer

Hypersensitivity pneumonitis is generally attributed to inhalational organic dust, commonly due to exposure to dust at occupation or hobbies. Hypersensitivity pneumonitis or extrinsic allergic alveolitis is an inflammatory syndrome of lungs resulting from immunologically induced inflammation secondary to various airborne allergens. It is relatively rare in childhood. Knowledge of classical HRCT finding of lungs and use of antigen specific IgG and IgM antibodies (despite the false positive and false negative) analysis can act as supportive evidence for making diagnosis of Hypersensitivity pneumonitis. We report a case of 4 yrs old girl child who despite being symptomatic, remained undiagnosed for 18-24 months, was on bronchodilator therapy suspecting pathophysiology being Hyperreactive airway disease but had recurrent episodes. When her hypoxic condition worsened later on, she was further investigated to rule out other differential, HRCT done was suggestive of childhood interstitial lung disease. The allergens test done for aspergillus species was positive in home environment and in her blood. She responded to steroids therapy and removal of offending agents from home environment. This case shows the importance of home environment in causing life threatening respiratory disease in children. She was diagnosed with Hypersensitivity pneumonitis, rare in childhood.

Infectious and Noninfectious Pulmonary Complications in Patients With Primary Immunodeficiency Disorders.

Primary immunodeficiency disorders (PIDs) are caused by 1 or more defects of the immune system. Patients are more likely to experience recurrent and/or severe infections and tend to develop a wide range of complications. Respiratory diseases are the main and initial manifestation in most cases and the most common complication. Pulmonary complications cause significant morbidity and mortality in patients with PIDs. Early diagnosis and appropriate treatment can prevent or at least slow the development of respiratory complications. Since the spectrum of pulmonary complications in PIDs is broad, we divided pulmonary complications into upper respiratory complications (eg, sinusitis, otitis media, and laryngeal angioedema) and lower respiratory complications (eg, pneumonia, bronchitis, bronchiectasis, interstitial lung diseases, organizing pneumonia, pulmonary adenopathies and malignancies, hyperreactive airway diseases, pulmonary dysgenesis, and adverse reactions to treatment). This review covers the main respiratory manifestations in patients with PIDs.

Ventricular tachycardia – An initial unusual presentation of sarcoidosis

A 42-year-old lady with a diagnosis of hyperreactive airway disease since 4 years treated with bronchodilators presented with monomorphic ventricular tachycardia with syncope requiring direct current (DC) cardioversion. Two-dimensional echocardiography with cardiac colour Doppler examination and magnetic resonance imaging (MRI) revealed left ventricular dilatation, systolic dysfunction with patchy areas of thickening and regional wall motion abnormality not specific to any particular vascular territory and advanced diastolic dysfunction.Review of records revealed persistently raised erythrocyte sedimentation rate which was previously ignored.Gadolinium contrast cardiac MRI revealed late gadolinium enhancement suggestive of myocarditis. Thoracic MRI revealed a mediastinal lymph node mass. A computed tomography (CT) directed lymph node biopsy confirmed sarcoidosis. She was offered implantable cardioverter-defibrillator device and immunosuppression therapy with prednisolone 1mg/kg/day.

Inflammatory Role of ROS-Sensitive AMP-Activated Protein Kinase in the Hypersensitivity of Lung Vagal C Fibers Induced by Intermittent Hypoxia in Rats.

Obstructive sleep apnea (OSA), manifested by airway exposure to intermittent hypoxia (IH), is associated with excess reactive oxygen species (ROS) production in airways, airway inflammation, and hyperreactive airway diseases. The cause-effect relationship for these events remains unclear. We investigated the inflammatory role of ROS-sensitive AMP-activated protein kinase (AMPK) in IH-induced airway hypersensitivity mediated by lung vagal C fibers (LVCFs) in rats. Conscious rats were exposed to room air (RA) or IH with or without treatment with N-acetyl-L-cysteine (NAC, an antioxidant), Compound C (an AMPK inhibitor), ibuprofen (a cyclooxygenase inhibitor), or their vehicles. Immediately after exposure (24 h), we found that intravenous capsaicin, phenylbiguanide, or α,β-methylene-ATP evoked augmented LVCF-mediated apneic responses and LVCF afferent responses in rats subjected to IH exposure in comparison with those in RA rats. The potentiating effect of IH on LVCF responses decreased at 6 h after and vanished at 12 h after the termination of IH exposure. The potentiating effect of IH on LVCF-mediated apneic and LVCF afferent responses was significantly attenuated by treatment with NAC, compound C, or ibuprofen, but not by their vehicles. Further biochemical analysis revealed that rats exposed to IH displayed increased lung levels of lipid peroxidation (an index of oxidative stress), AMPK phosphorylation (an index of AMPK activation), and prostaglandin E2 (a cyclooxygenase metabolite), compared with those exposed to RA. IH-induced increase in lipid peroxidation was considerably suppressed by treatment with NAC but not by compound C or ibuprofen. IH-induced increase in AMPK phosphorylation was totally abolished by NAC or compound C but not by ibuprofen. IH-induced increase in prostaglandin E2 was considerably prevented by any of these three inhibitor treatments. The vehicles of these inhibitors exerted no significant effect on the three IH-induced responses. These results suggest that 24-h IH exposure sensitizes LVCFs, leading to an exaggerated reflex and afferent responses to chemical stimulants in rats. Moreover, this IH-induced LVCF sensitization is mediated through a cascade of inflammatory responses in the airways involving increases in ROS, AMPK activation, and cyclooxygenase metabolite release.

NADPH Oxidase-Derived ROS Induced by Chronic Intermittent Hypoxia Mediates Hypersensitivity of Lung Vagal C Fibers in Rats

Obstructive sleep apnea (OSA), manifested by exposure to chronic intermittent hypoxia (CIH) and excess production of reactive oxygen species (ROS) in the airways, is associated with hyperreactive airway diseases. ROS, particularly when created by NADPH oxidase, are known to sensitize lung vagal C fibers (LVCFs), which may contribute to airway hypersensitivity pathogenesis. We investigated whether CIH augments the reflex and afferent responses of LVCFs to chemical stimulants and the roles of ROS and NADPH oxidase in such airway hypersensitivity. Rats were exposed to room air (RA) or CIH with/without daily treatment with MnTMPyP (a superoxide anion scavenger), apocynin (an NADPH oxidase inhibitor), or vehicle. At 16 h after their last exposure, intravenous capsaicin, adenosine, or α,β-methylene-ATP evoked an augmented apneic response in anesthetized rats with 14-days CIH exposure, compared to anesthetized rats with 14-days RA exposure. The augmented apneic responses to these LVCF stimulants were abolished by bilateral vagotomy or perivagal capsaicin treatment, which block LVCFs neural conduction and were significantly suppressed by treatment with MnTMPyP or apocynin, but not vehicle. Electrophysiological studies revealed that 14-days CIH exposure potentiated the responses of LVCFs to these stimulants. This effect was inhibited by treatment with MnTMPyP or apocynin treatment and was not seen in rats who received 7-days of CIH exposure. Biochemical analysis indicated that 14-days CIH exposure increased both lung lipid peroxidation, which is indicative of oxidative stress, and expression of the p47phox subunit in the membrane fraction of lung tissue, which is an index of NADPH oxidase activation. The former was prevented by treatment with either MnTMPyP or apocynin, while the later was prevented by treatment with apocynin only. These results suggest that 14-days CIH exposure sensitizes LVCFs in rats, leading to an exaggerated reflex and afferent responses to stimulants and that this sensitization is mediated via ROS generated by NADPH oxidase.

Relationship between oxygen saturation and clinical symptoms or signs in infants from 2 months to 12 months age with acute respiratory distress due to hyper reactive airway disease

Background: Facilities to measure SP02 are not available at all centers especially in the resource poor developing countries. This study is therefore important to identify a minimum set ofclinical signs that can reliably predict presence of hypoxemia in children with hyperreactive airway disease that can be used by health care provider to institute oxygen therapy. Methods: study was carried out as a single centre, prospective, observational study fromyear 2005 to 2007. A total of 51 children were studied equally divided in three groups depending upon oxygen saturation. A clinical scoring system was used which was generated after reviewing many studies and taking more practical aspect in relation to its use in peripheral set up. Result: The average age of the infants with oxygen saturation > 95% (Group A), 90–95% (Group B) and 95%) was ranging between 1 to 6, for group . (90–95%) was between 6 to 11 andfor group C ( 95% was 3, with Sp02 90–95% was 8 and with Sp02 <90% was 11 ( Table 2). Correlation coefficient was −0.906, as oxygen saturation was inversely related to clinical scoring of respiratory distress. Confidence interval at 95% for group A was 3.235±0.815,for group . was 8±0.672 andfor group C was 10.882 ± ft 917. The difference of clinical score between group A, group . and group C were statistically significant (p<0.001). Conclusion: Oxygen can be started for all babies with hyperreactive airway disease who are having clinical score of 7 or more and amount of oxygen to be increased as score increases from 7 to 14.

IgE mediates broncho-vascular remodeling after neonatal sensitization in mice.

The temporal origins of childhood asthma are incompletely understood. We hypothesize that allergen sensitization which begins in early infancy causes IgE-mediated airway and vascular remodeling, and airway hyper-responsiveness. Mice were sensitized with ovalbumin (OVA) without or with anti-IgE antibody from postnatal day (P) 10 through P42. We studied airway resistance in response to Methacholine (MCh) challenge, bronchoalveolar lavage fluid (BAL) inflammatory cell content, immunohistochemistry for inflammation, alpha-smooth muscle actin (alpha-SMA) and platelet/endothelial cell adhesion molecule (PECAM) proteins, and Western blotting for vascular endothelial growth factor (VEGF) protein. Compared to controls, mice treated with OVA had increased airway resistance (baseline: 192% of control; MCH 12 mg/mL 170% of control; P less than 0.0.5). OVA treatment also increased lung alpha-SMA, VEGF and PECAM compared to controls. Inflammatory cells in the BAL and perivascular and peribronchiolar inflammatory cell infiltrates increased over controls with OVA exposure. These changes were counteracted by anti-IgE treatment. We conclude that mice sensitized in early infancy develop an IgE-mediated hyper-reactive airway disease with airway and vascular remodeling. Preventive approaches in early infancy of at-risk individuals may reduce childhood asthma.

Anesthetic concerns in patients with hyper-reactive airways

Hyperreactive airway disease occurs due to acute viral or bacterial infections in children, and due to chronic bronchitis, Asthma or Emphysema in adults. Smoking and exposure to allergens may worsen the disease. Anaesthesia in these patients is associated with higher incidence of perioperative bronchospasm, postoperative laryngospam, breath holding, and hypoxia due to maldistribution of Ventilation and Perfusion. Smoking and exposure to allergens may worsen the outcome. Severe bronchospasm is a life threatening emergency. Selective β2 agonists form the main drug of choice for bronchospasm. Corticosteroids should be given early to reduce inflammation and mucosal oedema. For anaesthesia, Propofol, Vecuronium or Rocuronium, Halothane or Sevoflurane and Fentanyl are drugs of choice. Histamine releasing drugs like morphine and atracurium should be avoided. If ventilator support is required, Non invasive Pressure Support ventilation should be used first. However, Intubation and mechanical ventilation may become necessary, which however, may be associated with difficult weaning.

Spectrum of Phenotypic Manifestations of a Novel c1339A>C, pS447R Germline GATA2 Mutation

Background: Haploinsufficiency of GATA2 results in familial immunodeficiency and MDS/ AML. We identified a family with a novel c1339A>C, pS447R germline GATA2 mutation. Unlike most other disease-causing GATA2 mutations, this mutation occurred in the non-zinc finger domain. Methods: After due IRB approval, clinical and laboratory data were retrospectively abstracted.Results: Seven family members with the mutation are being followed at our institution. (Table 1), of whom two have MDS, one MDS/AML and one with isolated neutropenia. At the time of diagnosis 5/7(71%) pt had decreased monocyte count. 4/7(57%) patients had decreased NK cell count and/or function. Only 1/7(14%) patient had decreased CD4 count. 3/7(42%) patients had reduced B cell numbers and 5/7(71%) patients had persistent HPV warts. Other infections include invasive Absidia sinusitis, infectious mononucleosis, pertussis, and blood stream infections with S. maltophilia and S.aureus. One patient had the Emberger’s syndrome presenting with lymphedema and congenital pulmonary stenosis. Pulmonary manifestation included a patient each with decreased DCLO and hyperreactive airway disease. Genitourinary manifestations included pelvic kidney/dysplastic kidney, posterior urethral valve, dermoid cyst and hydrocele. Two female patients developed primary infertility. One patient had a history of appendicular carcinoid. 4/7(57%) patients have successfully undergone allogenic stem-cell transplantation.Conclusion: Germline GATA2 mutations are associated with a high frequency of MDS/AML. We describe a family with a non-zinc finger GATA2 mutation causing MDS/AML, with a spectrum of hematological and non-hematological manifestations, once again, highlighting the heterogeneity of this syndrome and expanding the genotype-phenotype correlation in this disease. Abstract 5614. Table#Age/sexHemDAbso . MonoCountAbso. CD4 TCellNK cyto-toxicityAbso. NK CountAbso.B cell CountInfectiousDermCoag/VascularCVS/LungOthersNo.137/MAMLSeverely DecreasedNormalAbsentSeverely DecreasedAbsentAbsidia S.maltop- hilia S.aureusHPV WartsITP -Hydrocele 10 hyperparathyroidismNo.231/FMDSDecreasedNormalAbsentDecreasedNormalInfectious MonoHPV Warts-Hyper- reactive airwayInfertilityNo.317/FMDSSeverely DecreasedNormalUnknownDecreasedDecreasedHerpes stomatitisHPV Warts-Dec-DCLOPosterior urethral valveNo.49/MNeutropeniaSeverely DecreasedNormalNormalNormalNormalHSV-1HPV Warts Embergers syndrome Pul. Stenosis Congenital dysplastic Rt. Kidney Pelvic Lt. KidneyNo.531/F-DecreasedNormalDecreasedNormalNormal- -Qualitative platelet defectNoneInfertilityNo.635/F-NormalNormalDecreasedDecreasedDecreasedPertussisHPV Warts--Dermoid appendicular carcinoid No.756/F-NormalNormalNormalNormalNormalFrequent PNA---- DisclosuresNo relevant conflicts of interest to declare.

Hyperreactive airway disease in adults: data from a national study in Lebanon.

Asthma and hyperreactive airway (HRA) disease are a major cause of health resource utilization and poor quality of life worldwide; its prevalence in adults may widely vary according to the definition used. It is mainly a childhood disease, but its natural history till adulthood is not well known. This is due to other confounding factors such as smoking and environmental factors that may lead to misdiagnose asthma as chronic obstructive pulmonary disease. Correct and timely diagnosis of asthma and HRA is important because it can be treated successfully and affected individuals may achieve good control of their disease. To evaluate the prevalence of asthma and HRA in Lebanese adults, their symptoms and predictors. A cross-sectional study using a multistage cluster sample was carried out in Lebanon, between October 2009 and September 2010.Lebanese residents aged 40 and above participated to the study; a post-bronchodilator spirometry was performed to confirm diagnosis. Out of 2201 individuals, 218 (99%) were considered to have HRA. The following factors were found associated with HRA in the Lebanese population: Northern (ORa: 3.54) and Bekaa Plain (ORa: 2.44)] versus other regions; occupational exposure to toxic gases and fumes (ORa: 2.08); heating home with wood (ORa: 1.75); having a family history of chronic respiratory disease (ORa: 2.19), a history of childhood lung problem (ORa: 5.53), and father smoking during childhood (ORa: 1.47). Added to these factors, HRA was also predicted by female gender (ORa: 1.81); lower education (ORa: 120); older age (ORa: 1.28) and low birth weight (ORa: 3.14). This is the first epidemiological study in Lebanon that determined physician diagnosed asthma prevalence and hyperreactive airway disease and their associated factors among Lebanese adults. It also provides useful contributions that local health organizations may use for national programming and a foundation for health researchers to pursue further study in asthma research. Public awareness about the increased risk of asthma associated with heating homes with wood and exposure to passive smoking should be raised; Lebanese policy makers should also generate higher efforts to implement and reinforce the smoking ban law in public places.