Wiskott-Aldrich Syndrome: Description of a New Gene Mutation With Normal Platelet Volume.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by an increased incidence of autoimmunity, malignancy, microthrombocytes with thrombocytopenia, eczema, and recurrent infections. In this case report, we present a novel mutation, hemizygous for c.1125_1129delTGGAC mutation in the WAS gene, and a unique clinical presentation. Our patient was initially diagnosed with a milk protein allergy after presenting with a lower gastrointestinal bleed, leukopenia, and thrombocytopenia with normal platelet volume. However, signs of vasculitis and detection of microthrombocytes required additional testing and consideration of WAS. This case report illustrates the importance of retaining a high index of clinical suspicion despite normal platelet volume, as well as adding to the growing number of known mutations associated with WAS.

Quantification of Aerosol Hydrofluoroalkane HFA-134a Elimination in the Exhaled Human Breath Following Inhaled Corticosteroids Administration.

Inhaled corticosteroids (ICS) and ß2-agonists are the primary pharmacotherapies of asthma management. However, suboptimal medication compliance is common in asthmatics and is associated with increased morbidity. We hypothesized that exhaled breath measurements of the aerosol used in the inhaled medications might prove useful as surrogate marker for asthma medication compliance. To explore this, 10 healthy controls were recruited and randomly assigned to ICS (Flovent HFA) or short acting bronchodilators (Proventil HFA). Both inhalers contain HFA-134a as aerosol propellant. Exhaled breath sampling and pulmonary function tests were performed prior to the inhaler medication dispersion, immediately after inhalation, then at 2, 4, 6, 8, 24, and 48 hours postadministration. At baseline, mean (SD) levels of HFA-134a in the breath were 252 (156) pptv. Immediately after inhalation, HFA-134a breath levels increased to 300 × 10(6) pptv and were still well above ambient levels 24 hours postadministration. The calculated ratio of forced expiratory volume in 1 second over forced vital capacity did not change over time following inhaler administration. This study demonstrates, for the first time, that breath HFA-134a levels can be used to assess inhaler medication compliance. It may also be used to evaluate how effectively the medicine is delivered.

Progression and prognostic indicators of bronchial disease in children with sickle cell disease.

PURPOSE: The pulmonary complications of sickle cell disease (SCD) are a leading cause of morbidity and mortality (MacLean et al. Am J Respir Crit Care Med 178:1055-1059, 2008; Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; National Heart, Lung, and Blood Institute, 2009). Despite this recognition, predictive markers of lung dysfunction progression remain elusive (Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; Platt et al. N Engl J Med 330:1639-1644, 1994; Caboot et al. Curr Opin Pediatr 20:279-287, 2008; Field et al. Am J Hematol 83:574-576, 2008; Shirlo et al. Peadiatr Respir Review 12:78-82, 2011). This study was designed describe the longitudinal progression and identify specific markers that influence bronchial disease in SCD. METHODS: A retrospective, chart review of 89 patients with SCD was conducted. All patients underwent spirometry in conjunction with body plethysmography as part of routine care. Eleven lung function variables were assessed, five of which were selected to establish patterns of normal, obstructive, restrictive, or mixed obstructive-restrictive physiology (Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; Field et al. Am J Hematol 83:574-576, 2008). RESULTS: In the unadjusted model, forced expiratory volume in one second (FEV1)% of predicted trended downward with age, while total lung capacity (TLC)% of predicted showed a bimodal distribution and carbon monoxide diffusion capacity corrected for hemoglobin (DLCOcor)% of predicted remained stable. Adjusting for acute chest syndrome (ACS) episodes, medication status, and growth velocity (GV), the final model demonstrated that the downward trend between FEV1% of predicted with age was further influenced by the latter two factors. CONCLUSIONS: Initial decline in FEV1% of predicted is associated with worsening pulmonary dysfunction over time. Independent of ACS episodes, the factors most influential on the progression of FEV1% predicted include the introduction of medications as well as the promotion of adequate prepubertal growth. Efforts to ensure normal prepubertal GV and treatment with bronchodilators, such as short-acting beta(2) agonists and inhaled corticosteroids (ICS), should be considered at an early age to delay progression of pulmonary dysfunction.