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Importance While intravenous magnesium decreases hospitalizations in refractory pediatric acute asthma, it is variably used because of invasiveness and safety concerns. The benefit of nebulized magnesium to prevent hospitalization is unknown. Objective To evaluate the effectiveness of nebulized magnesium in children with acute asthma remaining in moderate or severe respiratory distress after initial therapy. Design, Setting, and Participants A randomized double-blind parallel-group clinical trial from September 26, 2011, to November 19, 2019, in 7 tertiary-care pediatric emergency departments in Canada. The participants were otherwise healthy children aged 2 to 17 years with moderate to severe asthma defined by a Pediatric Respiratory Assessment Measure (PRAM) score of 5 or greater (on a 12-point scale) after a 1-hour treatment with an oral corticosteroid and 3 inhaled albuterol and ipratropium treatments. Of 5846 screened patients, 4332 were excluded for criteria, 273 declined participation, 423 otherwise excluded, 818 randomized, and 816 analyzed. Interventions Participants were randomized to 3 nebulized albuterol treatments with either magnesium sulfate (n = 410) or 5.5% saline placebo (n = 408). Main Outcomes and Measures The primary outcome was hospitalization for asthma within 24 hours. Secondary outcomes included PRAM score; respiratory rate; oxygen saturation at 60, 120, 180, and 240 minutes; blood pressure at 20, 40, 60, 120, 180, and 240 minutes; and albuterol treatments within 240 minutes. Results Among 818 randomized patients (median age, 5 years; 63% males), 816 completed the trial (409 received magnesium; 407, placebo). A total of 178 of the 409 children who received magnesium (43.5%) were hospitalized vs 194 of the 407 who received placebo (47.7%) (difference, −4.2%; absolute risk difference 95% [exact] CI, −11% to 2.8%];P = .26). There were no significant between-group differences in changes from baseline to 240 minutes in PRAM score (difference of changes, 0.14 points [95% CI, −0.23 to 0.50];P = .46); respiratory rate (0.17 breaths/min [95% CI, −1.32 to 1.67];P = .82); oxygen saturation (−0.04% [95% CI, −0.53% to 0.46%];P = .88); systolic blood pressure (0.78 mm Hg [95% CI, −1.48 to 3.03];P = .50); or mean number of additional albuterol treatments (magnesium: 1.49, placebo: 1.59; risk ratio, 0.94 [95% CI, 0.79 to 1.11];P = .47). Nausea/vomiting or sore throat/nose occurred in 17 of the 409 children who received magnesium (4%) and 5 of the 407 who received placebo (1%). Conclusions and Relevance Among children with refractory acute asthma in the emergency department, nebulized magnesium with albuterol, compared with placebo with albuterol, did not significantly decrease the hospitalization rate for asthma within 24 hours. The findings do not support use of nebulized magnesium with albuterol among children with refractory acute asthma. Trial Registration ClinicalTrials.gov Identifier:NCT01429415

Recently, this international task force reported the general considerations for bronchial challenge testing and the performance of the methacholine challenge test, a “direct” airway challenge test. Here, the task force provides an updated description of the pathophysiology and the methods to conduct indirect challenge tests. Because indirect challenge tests trigger airway narrowing through the activation of endogenous pathways that are involved in asthma, indirect challenge tests tend to be specific for asthma and reveal much about the biology of asthma, but may be less sensitive than direct tests for the detection of airway hyperresponsiveness. We provide recommendations for the conduct and interpretation of hyperpnoea challenge tests such as dry air exercise challenge and eucapnic voluntary hyperpnoea that provide a single strong stimulus for airway narrowing. This technical standard expands the recommendations to additional indirect tests such as hypertonic saline, mannitol and adenosine challenge that are incremental tests, but still retain characteristics of other indirect challenges. Assessment of airway hyperresponsiveness, with direct and indirect tests, are valuable tools to understand and to monitor airway function and to characterise the underlying asthma phenotype to guide therapy. The tests should be interpreted within the context of the clinical features of asthma.

Congenital central hypoventilation syndrome is a rare genetic disorder characterized by hypoventilation during sleep secondary to a blunted response to hypercapnia and hypoxia. The current case report describes developmentally normal four-year-old monozygotic twin boys who presented in infancy with variable presentations and clinical severity of congenital central hypoventilation syndrome. Both were managed with noninvasive positive pressure ventilation.

OBJECTIVES: To evaluate the factors that affect nebulizer efficiency and to compare the relative cost effectiveness of nebulized medications used in the treatment of cystic fibrosis (CF), delivered by four types of disposable jet nebulizers that are widely used in hospitals.DESIGN: The Hudson 1730 Updraft II, Baxter Misty-Neb, Marquest Whisper Jet (WJ), and Marquest Acorn II were evaluated in terms of respirable aerosol output (particles 5 µm or less), nebulizer dead (residual) volume (VD), and time for complete nebulization using saline, salbutamol and tobramycin at flows of 6 and 8 L/min. The respirable fraction (RF) was determined by laser diffraction, and drug output was calculated from the initial volume and concentration of the drug in the nebulizer minus the product of final drug concentration and the VDfollowing nebulization.COST ANALYSIS: The expected pulmonary deposition (DE) was estimated, and incorporated with the material and labour costs to determine the cost effectiveness of each type of nebulizer.RESULTS: With a DEgreater than two times that of the WJ at a cost of 2.4 times less, the Updraft II proved most efficient and cost effective of all the nebulizers evaluated in this study.CONCLUSIONS: The cost effectiveness of each nebulizer was determined by its efficiency, which in turn was predominantly related to its VDand RF at each flow. The efficiencies of these four devices were different and could not have been predicted from specifications provided by the respective manufacturers.

Burkholderia pseudomalleiis a pathogen identified with increasing frequency in the respiratory tracts of cystic fibrosis (CF) patients from endemic areas such as Southeast Asia and northern Australia. The following report describes the first known reported case in a CF patient from the Caribbean attending a North American CF clinic.

Limited data on the relative contributions of different routes of transmission for influenza virus are available. Person-to-person transmission is central to seasonal and pandemic spread; nevertheless, the modes of spread are a matter of ongoing debate. Resolution of this discussion is paramount to the development of effective control measures in health care and community settings. Using the guinea pig model, we demonstrated that transmission of influenza A/Panama/2007/1999 (H3N2) virus through the air is efficient, compared with spread through contaminated environmental surfaces (fomites). We also examined the aerosol transmission efficiencies of 2 human influenza virus A strains and found that A/Panama/2007/1999 influenza virus transmitted more efficiently than A/Texas/36/1991 (H1N1) virus in our model. The data provide new and much-needed insights into the modes of influenza virus spread and strain-specific differences in the efficiency of transmission.

SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 5 in this Series This section is written to provide guidance in interpreting pulmonary function tests (PFTs) to medical directors of hospital-based laboratories that perform PFTs, and physicians who are responsible for interpreting the results of PFTs most commonly ordered for clinical purposes. Specifically, this section addresses the interpretation of spirometry, bronchodilator response, carbon monoxide diffusing capacity ( D L,CO) and lung volumes. The sources of variation in lung function testing and technical aspects of spirometry, lung volume measurements and D L,CO measurement have been considered in other documents published in this series of Task Force reports 1–4 and in the American Thoracic Society (ATS) interpretative strategies document 5. An interpretation begins with a review and comment on test quality. Tests that are less than optimal may still contain useful information, but interpreters should identify the problems and the direction and magnitude of the potential errors. Omitting the quality review and relying only on numerical results for clinical decision making is a common mistake, which is more easily made by those who are dependent upon computer interpretations. Once quality has been assured, the next steps involve a series of comparisons 6 that include comparisons of test results with reference values based on healthy subjects 5, comparisons with known disease or abnormal physiological patterns ( i.e. obstruction and restriction), and comparisons with self, a rather formal term for evaluating change in an individual patient. A final step in the lung function report is to answer the clinical question that prompted the test. Poor choices made during these preparatory steps increase the risk of misclassification, i.e. a falsely negative or falsely positive interpretation for a lung function abnormality or a change …

[⇓][1] SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 3 in this Series [1]: #F7

This study analyzed the relationship between total respiratory resistance (Rrs) measured by forced oscillation technique and FEV 1 during histamine provocation test in 31 children between seven and 17 years of age. Rrs was measured at frequencies between 6 (R 6 ) and 26 Hz (R 26 ). (R 6 – R 26 )/R 26 was used as an index of frequency dependency of Rrs. A positive histamine test was defined as PC 20 less than 8 mg/ml. Seventeen subjects had a positive test, and all of these had increases from baseline of R 6 greater than 50 percent and (R 6 – R 26 /R 26 greater than 0.45. Of the 14 subjects whose PC 20 was greater than 8 mg/ml, only two had changes in R 6 and (R 6 —R 26 )/R 26 of this magnitude. These two subjects had changes in FEV 1 of 16 and 18 percent. There was a strong linear relationship between the changes in FEV 1 and both R 6 and (R 6 – R 26 )/R 26 from baseline to the final value at the end of the test (r = 0.87 and 0.91 respectively). In conclusion, this study demonstrated that the evaluation of airway reactivity by histamine challenge may be done by forced oscillation technique. It is easy to administer and may allow testing of children unable to perform spirometry.