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Rett syndrome is a neurodevelopmental disorder that manifests itself early in childhood, progresses with the evolution of characteristic clinical signs and symptoms and is confirmed by mutation in the methyl-CpG-binding protein 2 gene. Seizures are present in a majority of Rett patients. Respiratory dysrhythmia in the awake state is present in two-thirds of patients, leading in some cases to severe nonepileptic paroxysmal events. There are no optimal treatment recommendations thus far. The aim of this case study is to present the electro-clinical correlation of severe respiratory dysrhythmia mimicking seizures in 2 Rett patients and effective treatment with topiramate., (© The Author(s) 2013.)

Background and Aims: Respiratory complications represent an important adverse event of endoscopic procedures. We screened for respiratory complications after endoscopic procedures using a questionnaire and followed-up patients suggestive of respiratory infection., Method: In this prospective observational, multicenter study performed in Outpatient practices of gastroenterology we investigated 15,690 patients by questionnaires administered 24 hours after the endoscopic procedure., Results: 832 of the 15,690 patients stated at least one respiratory symptom after the endoscopic procedure: 829 patients reported coughing (5.28%), 23 fever (0.15%) and 116 shortness of breath (SOB, 0.74%); 130 of the 832 patients showed at least two concomitant respiratory symptoms (107 coughing + SOB, 17 coughing + fever, 6 coughing + coexisting fever + SOB) and 126 patients were followed-up to assess their respiratory complaints. Twenty-nine patients (follow-up: 22.31%, whole sample: 0.18%) reported signs of clinically evident respiratory infection and 15 patients (follow-up: 11.54%; whole sample: 0.1%) received therefore antibiotic treatment. Coughing or vomiting during the endoscopic procedure resulted in a 156.12-fold increased risk of respiratory complications (95% CI: 67.44 - 361.40) and 520.87-fold increased risk of requiring antibiotic treatment (95% CI: 178.01 - 1524.05). All patients of the follow-up sample who coughed or vomited during endoscopy developed clinically evident signs of respiratory infection and required antibiotic treatment while this occurred in a significantly lower proportion of patients without these symptoms (17.1% and 5.1%, respectively)., Conclusions: We demonstrated that respiratory complications following endoscopic sedation are of comparably high incidence and we identified major predictors of aspiration pneumonia which could influence future surveillance strategies after endoscopic procedures.

Background: Adenotonsillar hyperplasia (ATH) can lead to severe breathing disorders, such as impaired nasal breathing, mouth breathing, snoring and obstructive sleep apnea. In such cases ATH should be treated mostly by performing adenoidectomy and/or adenotonsillectomy. There is increasing evidence that anti-inflammatory medication (AIM) is effective in treating ATH-related breathing disorders., Objectives: The aim of this study was to provide evidence and recommendations for the use of AIM in the treatment of ATH-related breathing disorders., Methods: In this study 12 national pediatric sleep experts were included into a Delphi process and formulated indications and recommendations., Results: The use of AIM in the treatment of ATH-related breathing disorders is sufficiently supported by the results of randomized controlled trials and systematic reviews. Nasal beclometason and nasal mometason have been studied for the treatment of enlarged adenoids and nasal fluticason and oral montelukast for the treatment of obstructive sleep apnea. The use of AIM for first-line treatment should be restricted to selected indications, such as a characteristic patient age and exclusion of an acute upper respiratory tract infection. Evidence-based recommendations are given concerning indications, dosage, treatment duration and correct administration of AIM., Conclusions: Anti-inflammatory medications are simple and effective alternatives for the treatment of ATH-related breathing disorders. These guidelines are intended to promote the use of AIM by pediatricians in ambulatory care settings.

Our purpose was to evaluate the association of new benzodiazepine use relative to non-use with adverse clinical respiratory outcomes among older adults with chronic obstructive pulmonary disease (COPD). This was a retrospective population-based cohort study of Ontario, Canada, residents between 2003 and 2010. A validated algorithm was applied to health administrative data to identify adults aged 66 years and older with COPD. Relative risks (RRs) of several clinically important respiratory outcomes were examined within 30 days of incident benzodiazepine use compared with non-use, applying propensity score matching. New benzodiazepine users were at significantly higher risk for outpatient respiratory exacerbations (RR 1.45, 95% CI 1.36-1.54) and emergency room visits for COPD or pneumonia (RR 1.92, 95% CI 1.69-2.18) compared to non-users. Risk of hospitalisation for COPD or pneumonia was also increased in benzodiazepine users, but was nonsignificant (RR 1.09, 95% CI 1.00-1.20). There were no significant differences in intensive care unit admissions between the two groups and all-cause mortality was slightly lower among new versus non-users. Benzodiazepines were associated with increased risk for several serious adverse respiratory outcomes among older adults with COPD. The findings suggest that decisions to use benzodiazepines in older patients with COPD need to consider potential adverse respiratory outcomes., (©ERS 2014.)

Objective: To assess the clinical effect of medication monitoring using the West Wales Adverse Drug Reaction (ADR) Profile for Respiratory Medicine., Design: Single-site parallel-arm pragmatic trial using stratified randomisation., Setting: Nurse-led respiratory outpatient clinic in general hospital in South Wales., Participants: 54 patients with chronic respiratory disease receiving bronchodilators, corticosteroids or leukotriene receptor antagonists., Intervention: Following initial observation of usual nursing care, we allocated participants at random to receive at follow up: either the West Wales ADR Profile for Respiratory Medicine in addition to usual care ('intervention arm' with 26 participants); or usual care alone ('control arm' with 28 participants)., Main Outcome Measures: Problems reported and actions taken., Results: We followed up all randomised participants, and analysed data in accordance with treatment allocated. The increase in numbers of problems per participant identified at follow up was significantly higher in the intervention arm, where the median increase was 20.5 [inter-quartile range (IQR) 13-26], while that in the control arm was -1 [-3 to +2] [Mann-Whitney U test: z = 6.28, p<0.001]. The increase in numbers of actions per participant taken at follow up was also significantly higher in the intervention arm, where the median increase was 2.5 [1]-[4] while that in the control arm was 0 [-1.75 to +1] [Mann-Whitney U test: z = 4.40, p<0.001]., Conclusion: When added to usual nursing care, the West Wales ADR Profile identified more problems and prompted more nursing actions. Our ADR Profile warrants further investigation as a strategy to optimise medication management., Trial Registration: Controlled-trials.com ISRCTN10386209.

Background: Corticosteroid-induced myopathy is a well known clinical entity, and experimental studies showed decreased rate of protein synthesis and increased rate of protein breakdown in muscles of chronically treated animals., Objective: The present observational study was aimed to evaluate skeletal muscle functions in asthmatics and patients with other chronic respiratory diseases treated by inhaled or oral corticosteroids., Methods: Thirty six patients with respiratory diseases were included into the study. The physician-rated peripheral motor deficits scale, stepper test and ankle/wrist index were used for assessment of muscle functions. The effects of length of glucocorticoids intake on muscle functions were evaluated., Results: Sixty five per cent of patients using corticosteroids daily during 1 year and longer reported weakness in legs, and 20% of these patients demonstrated objective signs of the muscle weakness. The performance on the stepper test was significantly worse in patients chronically using corticosteroids in comparison with the control group (10.9 ± 3.4 steps vs 16.1 ± 2.4 steps per 10s, respectively; F=21.6, p<0.001). In addition, a proportion of patients using corticosteroids for at least 18 months were characterized by muscle hypotrophy at a dominant leg., Conclusion: Chronic intake of inhaled corticosteroids induces clinically significant decrease of muscle functions at least after 1-year of daily treatment., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Aerosol therapy continues to be considered as one of the cornerstones of the profession of respiratory care, even after 60 years. Aerosol therapy serves as a critical intervention for both exacerbations and chronic maintenance for a variety of respiratory care conditions. Aerosol therapy uniquely blends both the art and science of medicine together to produce the practical and necessary clinical outcomes for patients with respiratory diseases. This review was presented as part of the New Horizons Symposium on how to guide the scientific selection of an appropriate aerosol device.

Objectives: Analyze developments in the clinical adequacy of prescribing continuous home oxygen therapy to current regulations in the Andalusian Health Service., Methodology: Were reviewed in a previous study requirements and continuing new domiciliary oxygen therapy conducted from January 2008 to December 2009. It constituted a Monitoring Committee Multidisciplinary and turned to analyzing the appropriateness of prescribing after two pharmaceutical interventions from April 2011 to March 2012. Statistical analysis was performed by SPSS 15.0 for Windows, the dependent variable being the correct blade adjustment to the first prescription and then, and as independent prescribing different units. In cases in which the prescribing correct sheet, variables were analyzed mandatory., Results: 163 prescriptions were checked manually with a rate of compliance with the regulations of 66.30%, slightly higher than the results of the previous study (55.72% in 2008, 47.70% in 2009). The intervention did not achieve a greater degree the outlook for lack of financial and material resources, affecting one of the fundamental objectives were patient reviews., Conclusions: Pharmaceutical intervention has ensured that the prescription conforms to the rules and perform better, but has not been able to control the issue of revisions to rely on other medical and administrative units requesting increased technological and human resources to facilitate control., (Copyright © 2013 SEFH. Published by AULA MEDICA. All rights reserved.)

Background: Transient tachypnoea of the newborn (TTN) results from delayed clearance of lung liquid and is a common cause of admission of full term infants to neonatal intensive care units. The condition is particularly common after elective caesarean section. Conventional treatment involves appropriate oxygen administration and continuous positive airway pressure in some cases. Most infants receive antibiotic therapy. Hastening the clearance of lung liquid may shorten the duration of the symptoms and reduce complications., Objectives: To determine whether furosemide administration reduces the duration of oxygen therapy and respiratory symptoms and shortens hospital stay in term infants with transient tachypnoea of the newborn., Search Methods: An updated search was carried out in January 2013 of the following databases: The Cochrane Library issue 1, 2013 (CENTRAL, The Cochrane Central Register of Controlled Trials), PubMed, MEDLINE via Ovid, CINAHL via OVID and EMBASE., Selection Criteria: We included randomised and quasi-randomised controlled trials that compared the effect of furosemide administration versus placebo or no treatment in infants of less than seven days of age, born at 37 or more weeks of gestation with the clinical picture of transient tachypnoea of the newborn., Data Collection and Analysis: We extracted and analysed data according to the methods outlined in the latest Cochrane Handbook for Systematic Reviews of Interventions. Two review authors assessed trial quality in each potentially eligible manuscript and two review authors extracted data., Main Results: Our updated review includes two completed trials. Wiswell 1985 and Karabayir 2006 investigated 100 infants with transient tachypnoea of the newborn. Wiswell 1985 randomised 50 infants to receive either oral furosemide (2 mg/kg body weight at time of diagnosis followed by a 1 mg/kg dose 12 hours later if the tachypnoea persisted) or placebo. Karabayir 2006 randomised 50 infants to receive either intravenous furosemide (2 mg/kg body weight) or an equal volume of normal saline placebo. Neither trial reported on the need for respiratory support. Neither trial demonstrated a statistically significant impact of furosemide on transient tachypnoea of the newborn regarding duration of symptoms or length of hospitalisation., Authors' Conclusions: Oral or intravenous furosemide cannot be recommended as treatment for transient tachypnoea of the newborn and it should not be used unless additional data become available. This finding suggests that either furosemide is not effective in promoting resorption of lung fluid, or factors other than delayed resorption of this fluid contribute to the pathogenesis of transient tachypnoea of the newborn. The question remains as to whether furosemide given to the infant (or even to the mother before caesarean section) might shorten the duration of the illness. As elective caesarean section continues at a high level, these two interventions might be worthy of trials.

Mice deficient in the transcription factor methyl-CpG-binding protein 2 (Mecp2), a mouse model of Rett syndrome, display reduced CO2 chemosensitivity, which may contribute to their breathing abnormalities. In addition, patients with Rett syndrome and male mice that are null for Mecp2 show reduced levels of brain serotonin (5-HT). Serotonin is known to play a role in central chemosensitivity, and we hypothesized that increasing the availability of 5-HT in this mouse model would improve their respiratory response to CO2. Here we determined the apnoeic threshold in heterozygous Mecp2-deficient female mice and examined the effects of blocking 5-HT reuptake on the CO2 response in Mecp2-null male mice. Studies were performed in B6.129P2(C)-Mecp2(τm1.1Bird) null males and heterozygous females. In an in situ preparation, seven of eight Mecp2-deficient heterozygous females showed arrest of phrenic nerve activity when arterial CO2 was lowered to 3%, whereas the wild-types maintained phrenic nerve amplitude at 53 ± 3% of maximal. In vivo plethysmography studies were used to determine CO2 chemosensitivity in null males. These mice were exposed sequentially to 1, 3 and 5% CO2. The percentage increase in minute ventilation in response to increased inspired CO2 was less in Mecp2(-/y) than in Mecp2(+/y) mice. Pretreatment with citalopram, a selective 5-HT reuptake inhibitor (2.5 mg kg(-1) i.p.), 40 min prior to CO2 exposure, in Mecp2(-/y) mice resulted in an improvement in CO2 chemosensitivity to wild-type levels. These results suggest that decreased 5-HT in Mecp2-deficient mice reduces CO2 chemosensitivity, and restoring 5-HT levels can reverse this effect.

Acute methadone toxicity is a major public health concern in Iran. Methadone-intoxicated patients are in a great risk of recurrent or delayed respiratory arrest despite the prescription of initial doses of naloxone. This study aimed to evaluate the effectiveness of oral naltrexone in the management of acute methadone overdose in opioid-naive patients and check if it could be a substitute of continuous infusion of naloxone in maintaining adequate ventilation. In a randomized, double-blind, placebo-controlled study, a total of 54 opioid-naive patients with acute methadone toxicity were enrolled. The patients received either oral naltrexone or placebo capsules after awakening by naloxone. All patients underwent close monitoring of respiration. Frequency of respiratory depression or arrest, need for another dose of naloxone, duration of hospital stay, and adverse outcomes compared between the two groups. The incidence of respiratory depression was significantly less in those who had received naltrexone. Our results show that single oral dose of naltrexone is quite efficient in the prevention of recurrent or delayed respiratory arrest in opioid-naive methadone-intoxicated patients. It can shorten the duration of hospitalization and, as a consequence, decreased the risk of complications. Further studies are warranted before the generalization of this approach to other patient populations.

Pitt-Hopkins syndrome is a rare genetic form of severe psychomotor delay, caused by mutations in transcription cell factor-4 gene and characterized by distinctive dysmorphic features and abnormal breathing pattern. The current report describes the polygraphic features of the syndrome's typical breathing pattern in a patient both in wakefulness and in sleep. The control of these breathing alterations is important to prevent the neurological sequelae linked to chronic cerebral hypoxemia in early ages. No data are available on effective treatment options for breathing abnormalities of Pitt-Hopkins syndrome. The authors polygraphically documented a reduction of apneic and hypopneic phenomena, with a significant improvement in saturation values, after the introduction of sodium valproate.

Aim: This study investigated the effects of tiotropium bromide on chronic asthma patients with persistent obstructive ventilatory impairment (FEV1/FVC%<70%) like COPD., Methods and Subjects: Twenty-four patients (14 males, 10 females, mean age 64.3±10.7 years old) were enrolled. They were all treated with a high dose inhaled steroids and a long-acting β2-agonist. All patients had bronchial reversibility, normal diffusing capacity (DLCO) and no low attenuation areas in HRCT. This study examined the FEV1 at baseline and after inhalation of short-acting bronchodilators (400 μg salbutamol and 40 μg ipratropium, 15 minutes and 30 minutes after, respectively). Eleven patients agreed to take an additional treatment with tiotropium, and received 18 μg of tiotropium per daily for one year. The usual treatments were continued for 7 patients that did not agree to take tiotropium and for 6 patients who were ineligible for tiotropium due to co-morbidities. The FVC, FEV1, FEV1/FVC%, V50, and IC were compared between the two groups after one year., Results: FEV1 and V50 were significantly elevated after one year in the tiotropium-treated patients in comparison to those in the 13 subjects that did not receive tiotropium bromide, after adjusting for age, smoking and the values determined on enrollment. There was a positive correlation between the change of FEV1 30 min after ipratropium inhalation (short-term effect) and FEV1 one year after tiotropium inhalation (long-term effect)., Conclusion: Combination treatment with tiotropium, high dose steroids and long-acting β2 agonist inhalation provides improvement in the expiratory flow limitations of asthma patients with persistent obstructive ventilatory impairment.

Background: Chronic carbon black exposure in the work environment can cause both respiratory symptoms and changes in lung function. There is limited information on the respiratory effects of acute exposure to carbon black., Methods: Case report and literature review., Results: A 44-year-old man had intense exposure to carbon black when his crane ran into a truck with a trailer filled with carbon black. One week after this exposure he developed shortness of breath and cough with sputum production. These symptoms persisted and increased in intensity. Physical examination revealed expiratory wheezes when in the supine position. Pulmonary function tests revealed a mild obstructive ventilatory defect with a reduced FEV(1)/FVC ratio. The patient responded to treatment with fluticasone and salmeterol with a reduction in symptoms and improvement in his spirometry to a normal range., Conclusions: Acute exposure to carbon black can cause respiratory symptoms and an obstructive ventilatory defect. This presentation suggests a small airway disease which improved over time with inhaled steroids and long-acting beta-agonists. Patients with intense carbon black exposure following industrial accidents will need frequent evaluation to manage any related respiratory tract injury.

Background: The phenotypic variance observed in panic disorder (PD) appears to be best captured by a respiratory and non-respiratory panic subtype. We compared respiratory and non-respiratory panic subtypes across a series of external validators (temporal stability, psychiatric co-morbidity, treatment response) to determine whether subtypes are best conceptualized as differing: (1) only on their symptom profiles with no other differences between them; (2) on a quantitative (i.e. severity) dimension only; or (3) qualitatively from one another., Method: Data from a large epidemiological survey (National Epidemiologic Survey on Alcohol and Related Conditions) and a clinical trial (Cross-National Collaborative Panic Study) were used. All analytic comparisons were examined within a latent class framework., Results: High temporal stability of panic subtypes was observed, particularly among females. Respiratory panic was associated with greater odds of lifetime major depression and a range of anxiety disorders as well as increased treatment utilization, but no demographic differences. Treatment outcome data did not suggest that the two PD subtypes were associated with differential response to either imipramine or alprazolam., Conclusions: These data suggest that respiratory and non-respiratory panic represent valid subtypes along the PD continuum, with the respiratory variant representing a more severe form of the disorder.

The discovery of ghrelin has resulted in the development of potential therapeutics for cachexia caused by multiple underlying diseases. When chronic respiratory diseases progress to their advanced stages, cachexia often occurs, thereby worsening the patient's prognosis. A small clinical trial that enrolled cachectic patients with chronic respiratory disease revealed that administration of ghrelin improved their nutritional status and exercise tolerance. Short-term administration of ghrelin was found to be safe and tolerated with adverse events, including suffusion, sleepiness, peristalsis, hunger, and sweating. Further large-scale and long-term clinical trials are needed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy of inhaled salbutamol, a beta-2 adrenergic agonist, for the treatment of transient tachypnea of the newborn (TTN) and to determine whether inhaled salbutamol is safe in newborn infants., Study Design: Inhaled salbutamol or normal saline solution was administered to 54 infants with gestational ages ranging from 34 to 39 weeks and TTN. The response to salbutamol therapy was evaluated by determining respiratory rate, clinical score of TTN, level of respiratory support, and fraction of inspired oxygen before and at 30 minutes and 1 and 4 hours after salbutamol nebulization., Results: Among the 54 infants with TTN, 32 received salbutamol and 22 received normal saline solution. After one dose, the salbutamol group showed significant improvements in respiratory rate, clinical score of TTN, fraction of inspired oxygen, and level of respiratory support (P < .05). After treatment, the mean pH, partial pressure of arterial oxygen, and partial pressure of arterial carbon dioxide values were better in the salbutamol group when compared with the placebo group (P < .05). Duration of hospitalization in the neonatal intensive care unit was also shorter for the salbutamol group (P < .05)., Conclusion: Inhaled salbutamol treatment was effective with respect to both clinical and laboratory findings of TTN and without adverse events., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: The purpose of this research is to develop and evaluate methods for conducting cluster randomised trials in a primary care database that contains electronic patient records for large numbers of family practices. Cluster randomised trials are trials in which the units allocated represent groups of individuals, in this case family practices and their registered patients. Cluster randomised trials often suffer from the limitation that they include too few clusters, leading to problems of insufficient power and only imprecise estimation of the intraclass correlation coefficient, a key design parameter. This difficulty might be overcome by utilising databases that already hold electronic patient records for large numbers of practices. The protocol describes one application: a study of antibiotic prescribing for acute respiratory infection; a second protocol outlines an intervention in a less frequent chronic condition of public health importance, stroke., Methods/design: The objective of the study is to implement a cluster randomised trial to test the effectiveness of an electronic record-based intervention at achieving a reduction in antibiotic prescribing at consultations for respiratory illness in patients aged 18 and 59 years old in intervention family practices as compared with controls. Family practices will be recruited from the practices that presently contribute data to the UK General Practice Research Database (GPRD). Following randomisation, electronic prompts will be installed remotely at intervention practices to promote adherence with evidence-based standards of medical practice. The intervention was developed through qualitative research at non-intervention practices. Data for outcome assessment will be obtained from anonymised electronic patient records that are routinely collected into GPRD. This protocol outlines the proposed study designs, data sources, sample size requirements, analysis methods and dissemination plans. Ethical issues are also discussed., Discussion: Results from this study will provide methodological evidence concerning the use of electronic patient records and databases for implementing cluster randomised trials in primary care. The study will also provide substantive findings in respect of electronic record-based interventions to reduce antibiotic prescribing in primary care., Trial Registration: Current Controlled Trials ISRCTN 47558792.

Background: The aerosolization of perfluorocarbons or surfactant has emerged as a feasible alternative to instillation, for the treatment of experimental respiratory distress syndrome. However, the biophysical properties that make these compounds useful in such therapies, significantly affect the performance of nebulizers. Therefore, in vitro studies are required to assess the suitability of new aerosolization technologies for use with these compounds., Methods: The aim of the present in vitro study was to investigate the influence of the biophysical properties of perfluorocarbons (PFD, FC75, and PFOB) and a natural porcine surfactant, Curosurf®; on aerosolization and to assess the suitability of three intratracheal inhalation catheters (IC) with different air flow rates (IC-1.23, IC-1.1, IC-1.4) coupled to a jet nebulizer, for aerosol delivery of these compounds., Results: With IC-1.23 significantly higher aerosol production rates were achieved (p < 0.0001), ranging between 6.05 ± 0.17 mL/min (FC75) and 1.94 ± 0.09 mL/min (Curosurf®), and lower percentage losses of the compound (5-21%), compared to IC-1.1 and IC-1.4 catheters. The lowest aerosolization rates were produced with IC-1.4 ranging from 0.58 ± 0.02 mL/min (FC75) to 0.14 ± 0.01 mL/min (Curosurf®), and this catheter also resulted in the highest percentage losses (25-60%). The mass median aerodynamic diameter (MMAD) ranged between 0.77 μm (PFD) and 8.29 μm (Curosurf®) with IC-1.1, whereas higher MMAD values, of between 4.84 μm (FC75) and 13.42 μm (PFOB), were observed with IC-1.23. Regardless of the catheter used during aerosolization, the perfluorocarbon with the highest kinematic viscosity showed the lowest aerosolization and emission rates and vice versa, which reveals the substantial contribution of this parameter that should accordingly be considered in the design of perfluorocarbon aerosol drug delivery systems., Conclusions: Jet aerosolization of perfluorocarbons or surfactant with the intratracheal inhalation catheters seems to be a suitable method for treating experimental respiratory distress syndrome, because it delivers relatively high doses of perfluorocarbons and surfactant to the lungs in a respirable size droplets.

Background: H(2)S synthesis inhibitors (HSSI) have been shown to impact respiratory control. For instance, the HSSI hydroxylamine (HA) decreases the respiratory discharge rate from isolated medullary sections, and HA in addition to other HSSIs propargylglycine and amino-oxyacetic acid (AOAA) have been found to reduce hypoxic responsiveness., Objectives: The aim of this study was to determine if administration of HSSIs could improve respiratory stability in an intact organism prone to recurrent central apneas., Methods: Saline and HSSI compounds were administered to C57BL/6J mice (n = 24), a strain predisposed to recurrent central apneas, prior to measurement of hypoxic and posthypoxic ventilatory behavior., Results: Administration of HA and AOAA resulted in a significantly smaller percentage of animals expressing one or more apneas during reoxygenation compared to saline control, and animals given AOAA demonstrated a smaller coefficient of variation for frequency during reoxygenation, a marker suggesting greater respiratory stability. This occurred despite varying effects of the three HSSI compounds on hypoxic ventilatory response., Conclusions: Instability and pause expression are improved by targeting H(2)S synthesis, an effect not predicted by effects on hypoxic responsiveness., (Copyright © 2011 S. Karger AG, Basel.)

The purpose of this work was to improve the drug dispensing process at the National Institute of Respiratory Diseases of Mexico by applying the six sigma methodology, identifying the non-value added activities as well as the areas of opportunity, in order to make proposals to ensure the supply of prescription drugs to the patient in a timely manner. Seven variables were defined and three indicators were generated, which were implemented in three clinical services of the Institute to measure the current performance of the drug distribution process. With the obtained results, a proposed set of eight improvements were subsequently implemented in a pilot program.

This paper explores the relationship between insular stroke and the disruption of tobacco use. A functional analysis of the role of the insula in maintaining homeostasis suggests that the insula monitors hypoxia and applies dyspnea to motivate the individual to regulate breathing. From its' early usage, nicotine has been used to treat respiratory disorders. It increases respiratory drive, promoting better breathing. Insular stroke likely interferes with this self-regulation. A new self-medication model is proposed for tobacco use. The effect on public policy is discussed., ((c) 2010 Elsevier Ltd. All rights reserved.)

Background: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) represent the leading causes of death in systemic sclerosis (SSc). Screening for these complications has assumed greater importance, but is not universal. The aim of this study is to determine the self-reported screening, diagnosis and treatment practices of rheumatologists and respiratory physicians for SSc-related lung disease., Methods: Email survey of 270 rheumatologists and 600 respiratory physicians., Results: Responses were received from 42 (16%) rheumatologists and 68 (11%) respiratory physicians. Of SSc patients seen by rheumatologists, 17% had ILD and 7.5% had a diagnosis of PAH compared with 31% and 21% for respiratory physicians. Forty per cent of all physicians screened asymptomatic SSc patients without a known diagnosis of ILD or PAH less than annually or not at all. The most commonly used screening investigations were pulmonary function tests (PFT) (95%) and transthoracic echocardiogram (TTE) (78%). In suspected ILD, both groups used high-resolution computed tomography scans and PFT in >90% of patients. In suspected PAH, both used TTE and PFT (>90%); right heart catheterisation was used by only 50% of physicians. In treatment of ILD, rheumatologists used intravenous (IV) cyclophosphamide more often (CYC) (59% vs 28%, P= 0.003) and more respiratory physicians used oral CYC (44% vs 28%, P= 0.012). In PAH, more respiratory physicians used warfarin (68% vs 40%, P= 0.006). Only approximately 65% of physicians had used specific PAH therapy, which may reflect lack of access to a designated PAH treatment centre., Conclusion: The heterogeneity of responses revealed in this study raises the importance of screening, diagnosis and treatment algorithms in the management of this potentially life-threatening disease.

Objectives: To emphasize the safety and efficacy of theophylline in chronic inflammatory respiratory diseases. To mention its immunomodulatory effects., Data Sources: PubMed search using the keywords: theophylline, histone deacetylase, antiinflammatory, asthma, chronic obstructive pulmonary disease (COPD), corticoresistance., Results: Theophylline is a methylxantine, that inhibits phosphodiesterase (PDE), induces histone deacetylase and antagonizes adenosine. Its main effect is to relax airway smooth muscle. The immunomodulatory effects of theophylline are obtained at low plasma concentrations (less than 10 mg/L). The combination of inhaled corticoesteroids and theophylline exerts a synergistic antiinflammatory effect that improves asthma control and reduces COPD exacerbations. Histones are a group of transcriptional cofactors involved in chromatin remodeling. Histone deacetylases (HDACs) suppress inflammatory gene expression. In patients with COPD and severe asthma there is a reduction in HDAC-2 secondary to the increased oxidative and nitrative stress. HDAC-2 is required by corticosteroids to switch off activated inflammatory genes, then its reduction favors corticosteroid resistance. Theophylline via HDAC-2 induction and PDE inhibition, suppresses inflammatory gene expression, and inhibits free oxygen radicals production., Conclusions: Theophylline at low plasma concentrations exerts antiinflammatory effects, restoring corticosteroid sensitivity in COPD and severe asthma.

Mechanical ventilation is considered a supportive, nontherapeutic technology used to perform the work of breathing for patients who are unable to do so on their own. In neonatology, mechanical ventilation is often used for premature neonates who are unable to sustain ventilation because of reduced functional residual capacity due to surfactant deficiency. Mechanical ventilation is thus an attempt to mimic the respiratory system's physiological function of gas exchange until the respiratory system reaches maturation. In pediatrics, mechanical ventilation is rarely used for acute respiratory distress syndrome as shown by Dahlem et al. in 2003 who found that only 9.9% of cases of respiratory failure in PICU was caused by ARDS. For this reason, ventilatory techniques in PICU are very heterogenous from the assisted to the most aggressive controlled modes associated with ventilator maneuvers. There are no specific guidelines for the use of mechanical ventilation in children and the low number of infants with ARDS in PICU makes it difficult to run randomized controlled trials in this population. Thus the algorithms are based on the results of either adult or neonatal studies. The advantage of extrapolating data from the neonatal evidence relates mainly to the prevention of ventilator induced lung injury (e.g., CPAP, HFOV, NIV, permissive hypercapnia, surfattant), of which neonatologists are particularly expert.

Background: Breath-holding attacks are common during childhood. Iron supplementation has been claimed to reduce the frequency or severity, or both, of breath-holding attacks in children., Objectives: To assess the effect of iron supplementation on the frequency and severity of breath-holding attacks in children., Search Strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, CINAHL and the metaRegister of Controlled Trials (up to April 2009). We scanned references of included trials. Pharmaceutical companies manufacturing oral iron supplements and some trial authors were contacted for any unpublished data or trials., Selection Criteria: Randomised and quasi-randomised controlled trials comparing iron supplementation with placebo or no therapy in children < 18 years with recurrent (more than three) breath-holding episodes. These were reported by an observer., Data Collection and Analysis: The primary outcome was reduction in the frequency (number over time) or severity (leading to cessation of loss of consciousness or convulsive movements), or both, of breath-holding attacks. Two authors (AZ and NO) independently selected studies and extracted data. Study authors were contacted for missing data, where necessary. Risk of bias was assessed using domain-based evaluation. In the presence of low heterogeneity, a fixed-effect meta-analysis was performed with pooled results presented as odds ratios (OR) and 95% confidence intervals (CIs)., Main Results: Two trials (87 children) fulfilled the inclusion criteria. In these trials, iron supplementation significantly reduced the frequency of breath-holding attacks in children (OR 76.48; 95% CI 15.65 to 373.72; P < 0.00001). A meta-analysis that solely examined iron supplementation causing complete resolution of breath-holding attacks maintained this significance (OR 53.43; 95% CI 6.57 to 434.57; P = 0.0002)., Authors' Conclusions: Iron supplementation (at 5 mg/kg/day of elemental iron for 16 weeks) appears to be useful in reducing the frequency and severity of breath-holding attacks. Supplementation is of particular benefit in children with iron deficiency anaemia, responses correlating with the improvements in haemoglobin values. Iron may still be of assistance in children who are not anaemic or who have low, normal haemoglobin levels. Further high-quality randomised control trials of iron supplementation to treat breath-holding attacks in children are required.

The macrolides are antibiotics that, besides their anti-bacterial action, have an anti-inflammatory effect, by decreasing the activity of the immune cells and bacteria cell changes. An increase the survival of patients suffering from diffuse panbronchiolitis was already seen in the 1980s, after being treated with erythromycin. Currently, the use of macrolides in various chronic inflammatory diseases has increased significantly. Clinical improvements associated to the administration of macrolides have been observed in diseases such as, cystic fibrosis, asthma, and bronchiectasis. However, despite the apparent clinical benefit they seem to provide, the published results up until now are controversial and conclusive results are unable to be obtained. This means that further clinical trials are necessary to confirm or refute the long-term use of these drugs, which are not free of adverse effects, mainly the appearance of resistant bacteria., (Copyright 2009 SEPAR. Published by Elsevier Espana. All rights reserved.)

Objective: To compare the efficacy and adverse effects of aerosolized L-epinephrine vs budesonide in the treatment of post-extubation stridor., Study Design: Randomized controlled trial., Setting: Pediatric intensive care unit (PICU) of a tertiary teaching and referral hospital., Subjects: Sixty two patients with a stridor score ?4 following extubation., Intervention: Patients were randomized to receive either aerosolized L-epinephrine (n=32) or budesonide (n =30). Respiratory rate, heart rate, stridor score, blood pressure and oxygen saturation were recorded from 0 min to 24 hours., Outcome Measures: Stridor score remaining at >4, need for renebulization and reintubation between 20 min to 24 hours were primary outcome measures. Tachycardia (HR > normal for age), hypertension (BP >95th centile for age) and hypoxia (SpO2 < 92% for 5 min) were secondary outcome measures., Results: Both drugs showed a significant and comparable decline in the median (95% CI) stridor scores from baseline to 60 min [4 (4.10-4.50) to 2.00 (1.46-2.67) for budesonide vs 4 (4.12-5.00) to 2.00 (1.31 -2.75) for epinephrine]. At 2 hours, the stridor scores were significantly lower in the epinephrine as compared to budesonide group [0.00 (0.69-1.81) vs 3.00(1.75-3.32); P =0.02)]. However, the proportion of patients with stridor score >4 at any time between 20 min to 24 hrs (53.3% vs 53.1%; P=0.99), need for renebulization (40% vs 43.8%; P=0.76) and reintubation (20% vs 25%, P=0.638), and adverse effects were similar in both groups., Conclusions: Both aerosolized L-epinephrine and budesonide were equally effective in their initial therapeutic response in post-extubation stridor. However, epinephrine showed a more sustained effect.

The management of refractory asthma remains a compelling clinical problem that contributes significantly to the morbidity of patients as well as posing a financial burden to the health system. Treatment failure in this group of patients is associated with continued airway inflammation and dampening of the inflammatory cascade is the focus of much research in this area. Continued airway inflammation has been associated with higher patient morbidity and is being increasingly measured using markers of systemic and local inflammation in order to target therapy more effectively. This review focuses on the published evidence for both established and novel treatments in refractory asthma that act to control this pathological inflammatory process. No clear treatment yet exists to control this process and further research into inhibiting newly elucidated inflammatory pathways or new drugs more effectively or accurate targeting existing pathways are discussed along with the clinical evidence and the relative merits of each treatment., (2009 Elsevier Masson SAS. All rights reserved.)

This European Respiratory Society task force has reviewed the evidence for paediatric medicines in respiratory disease occurring in adults and children. We describe off-licence use, research priorities and ongoing studies. Off-licence and off-label prescribing in children is widespread and potentially harmful. Research areas in asthma include novel formulations and regimens, and individualised prescribing. In cystic fibrosis, future studies will focus on screened infants and robust outcome measures are needed. Other areas include new enzyme and antibiotic formulations and the basic defect. Research into pneumonia should include evaluation of new antibacterials and regimens, rapid diagnostic tests and, in pleural infection, antibiotic penetration, fibrinolytics and surveillance. In uncommon conditions, such as primary ciliary dyskinesia, congenital pulmonary abnormalities or neuromuscular disorders, drugs indicated for other conditions (e.g. dornase alfa) are commonly used and trials are needed. In neuromuscular disorders, the beta-agonists may enhance muscle strength and are in need of evaluation. Studies of antibiotic prophylaxis, immunoglobulin and antifungal drugs are needed in immune deficiency. We hope that this summary of the evidence for respiratory medicines in children, highlighting gaps and research priorities, will be useful for the pharmaceutical industry, the paediatric committee of the European Medicines Agency, academic investigators and the lay public.

Introduction: Distinguishing community acquired pneumonia (CAP) from chronic obstructive pulmonary disease (COPD) exacerbation is a challenging task, since fever, productive cough, dyspnea, and leukocytosis are all common features of both conditions. Moreover, chest X-ray might not be sensitive enough. It is therefore quite common for physicians to prescribe unnecessary antibiotics for COPD exacerbation, leading to resistant bacteria and other related adverse affects., Aim: To study whether CRP levels upon admission and the delta in CRP levels following initiation of antibacterial treatment, could provide an efficient tool for distinguishing CAP from COPD exacerbation., Methods: The study group included 36 COPD exacerbation and 49 CAP patients, admitted to a single Internal Medicine department during the years 2004-2006. All patients were treated with cephalosporins and macrolides upon admission., Results: CRP levels upon admission were significantly higher among CAP patients than among COPD exacerbation patients (111.5+/-104.4 vs. 34.9+/-28.6 mg/l, p<0.0001). CRP levels on the second day of hospitalization, following antibiotic administration to all patients, made a sharp incline in 36.7% of CAP patients compared to only 5.9% of COPD exacerbation patients (p=0.005), and remained unchanged in 61.8% of COPD patients compared to 16.3% of CAP patients (p=0.0006)., Conclusions: CRP levels upon admission and the delta in CRP levels following initiation of antibacterial treatment could provide an efficient tool for distinguishing CAP from COPD exacerbation., (2009 European Federation of Internal Medicine.)

Background: Post-extubation stridor may prolong length of stay in the intensive care unit, particularly if airway obstruction is severe and re-intubation proves necessary. Some clinicians use corticosteroids to prevent or treat post-extubation stridor, but corticosteroids may be associated with adverse effects ranging from hypertension to hyperglycaemia, so a systematic assessment of the efficacy of this therapy is indicated., Objectives: To determine whether corticosteroids are effective in preventing or treating post-extubation stridor in critically ill infants, children, or adults., Search Strategy: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL and reference lists of articles. The most recent searches were conducted in January 2009., Selection Criteria: Randomized controlled trials comparing administration of corticosteroids by any route with placebo in infants, children, or adults receiving mechanical ventilation via an endotracheal tube in an intensive care unit., Data Collection and Analysis: Three review authors independently assessed trial quality and extracted data., Main Results: Eleven trials involving 2301 people were included: six in adults, two in neonates, three in children. All but one examined use of steroids for the prevention of post-extubation stridor; the remaining one concerned treatment of existing post-extubation stridor in children. Patients were drawn from heterogeneous medical/surgical populations. Dexamethasone given intravenously at least once prior to extubation was the most common steroid regimen utilized (uniformly in neonates and children). In neonates the two studies found heterogeneous results, with no overall statistically significant reduction in post extubation stridor (RR 0.42; 95% CI 0.07 to 2.32). One of these studies was on high-risk patients treated with multiple doses of steroids around the time of extubation, and this study showed a significant reduction in stridor. In children, the two studies were clinically heterogeneous. One study included children with underlying airway abnormalities and the other excluded this group. Prophylactic corticosteroids tended to reduce reintubation and significantly reduced post-extubation stridor in the study that included children with underlying airway abnormalities (N = 62) but not in the study that excluded these children (N = 153). In six adult studies (total N = 1953), the use of prophylactic corticosteroid administration did not significantly reduce the risk of re-intubation (RR 0.48; 95% CI 0.19 to 1.22). While there was a significant reduction in the incidence of post extubation stridor (RR 0.47; 95% CI 0.22 to 0.99), there was significant heterogeneity (I(2)=81%, X(2)=26.36, df=5, p<0.0001). Subgroup analysis revealed that post extubation stridor could be reduced in adults with a high likelihood of post extubation stridor when corticosteroids were administered as multiple doses begun 12-24 hours prior to extubation compared to single doses closer to extubation; the test for interaction for multiple versus single doses indicated RRR 0.22 (95% CI 0.10 to 0.47) for stridor with multiple doses. Side effects were uncommon and could not be aggregated., Authors' Conclusions: Using corticosteroids to prevent (or treat) stridor after extubation has not proven effective for neonates or children. However, given the consistent trends towards benefit, this intervention does merit further study, particularly for high risk children or neonates. In adults, multiple doses of corticosteroids begun 12-24 hours prior to extubation do appear beneficial for patients with a high likelihood of post extubation stridor.

Purpose: Respiratory symptoms account for the majority of drug prescriptions in the first year of life. We investigated the influence of child, parent and physician factors on drug prescriptions for respiratory symptoms in primary care in infancy., Methods: Infants participated in the WHeezing Illnesses STudy LEidsche Rijn (WHISTLER), a prospective birth cohort on respiratory illnesses. Outcome was defined as having received a prescription of antibiotics or of anti-asthma medication for respiratory symptoms by a physician., Results: Nearly 60% of all children ever visited a physician for respiratory symptoms during the first year of life, of which 40% received a prescription. Every extra day with symptoms during the month before consultation and each extra visit to a physician were associated with a higher chance for prescription (respectively odds ratios (OR) 1.07/2.63, 95% confidence intervals (CI) 1.02-1.12/1.83-3.76). Further, we found a higher chance for drug prescribing for boys (2.7, 2.0-3.7), children attending day care (1.17, 1.09-1.25), mothers with higher education (2.3, 1.2-4.6), working mothers (4.5, 0.9-22.0) and older mothers (years) (1.09, 1.02-1.16). Furthermore, physicians' years of experience was a determinant for receiving a prescription (2.5, 1.1-6.0). Accounting for symptoms and visits as strong predictors of prescribing, infant gender and day care attendance were still predictors. Furthermore, infant gender, day care attendance, family history of asthma and physicians' years of experience were independent determinants of the number of prescriptions besides symptoms and visits., Conclusion: In young infancy, besides the severity of symptoms there are child, physician and particularly maternal characteristics that influence the decision of general practitioners to prescribe drugs for respiratory symptoms., ((c) 2009 John Wiley & Sons, Ltd.)

Multiple respiratory abnormalities can be found in anxiety disorders, especially in panic disorder (PD). Individuals with PD experience unexpected panic attacks, characterized by anxiety and fear, resulting in a number of autonomic and respiratory symptoms. Respiratory stimulation is a common event during panic attacks. The respiratory abnormality most often reported in PD patients is increased CO2 sensitivity, which has given rise to the hypothesis of fundamental abnormalities in the physiological mechanisms that control breathing in PD. There is evidence that PD patients with dominant respiratory symptoms are more sensitive to respiratory tests than are those who do not manifest such symptoms, and that the former group constitutes a distinct subtype. Patients with PD tend to hyperventilate and to panic in response to respiratory stimulants such as CO2, triggering the activation of a hypersensitive fear network. Although respiratory physiology seems to remain normal in these subjects, recent evidence supports the idea that they present subclinical abnormalities in respiration and in other functions related to body homeostasis. The fear network, composed of the hippocampus, the medial prefrontal cortex, the amygdala and its brain stem projections, might be oversensitive in PD patients. This theory might explain why medication and cognitive-behavioral therapy are both clearly effective. Our aim was to review the relationship between respiration and PD, addressing the respiratory subtype of PD and the hyperventilation syndrome, with a focus on respiratory challenge tests, as well as on the current mechanistic concepts and the pharmacological implications of this relationship.

Introduction: Progress to democracy in South Africa in 1994 was followed by the adoption of a primary health care approach with free access for all. State health facilities serve 80% of the population, and a private sector comprising general practitioners, specialists and private hospitals, serves the remainder. NATIONAL POLICIES AND MODELS: There are national prescribing guidelines for common diseases, and these specify the medicines on the Essential Drugs List that are available at primary care facilities for respiratory diseases including asthma, COPD, pneumonia and tuberculosis., Epidemiology: Asthma prevalence is average among children (13%) but morbidity is high. COPD rates are high owing to concurrent risk factors of smoking (in both men and women), occupational exposures, biomass fuel use and previous lung infections including tuberculosis. Tuberculosis and HIV are rampant, and together with pneumococcal co-infection account for considerable mortality., Access to Care: Primary care facilities are within reach of most communities, but major barriers to care include loss of income, waiting times in clinics, cost of transportation, and inconvenient hours., Facilities Available: The country is divided into districts each served by a hospital, several community health centres and many fixed or mobile clinics. The latter provide predominantly nurse-led care by nurse practitioners with additional qualifications. Some clinics and most community health centres are served by doctors. Referrals are made to secondary and tertiary hospitals served by specialists., Future: Innovations to address staff shortages include the creation of the specialty of family medicine for physicians and development of the clinical associate who is trained to perform a limited clinical role, as well as in-service on-site training of nurses through programmes of integrated care for infectious and chronic diseases. There is an urgent need to address low staff morale and medical migration resulting from a decade of poor leadership and AIDS denialism., Conclusions: The structures and policies for primary care in South Africa provide some grounds for optimism that services may begin to match the promise of quality care for all, but the burden of disease and resource constraints - particularly in terms of qualified personnel - mitigate against an early delivery of this promise.