Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations.

INTRODUCTION: Oral corticosteroids are the cornerstone of acute asthma management in the emergency department. Recent evidence has raised doubts about the efficacy of this treatment in preschool-aged children with viral-induced wheezing and in smoking adults. The aims of the study were to: (1) document the magnitude of response to oral corticosteroids in children presenting to the emergency department with moderate or severe asthma; (2) quantify potential determinants of response to corticosteroids and (3) explore the role of gene polymorphisms associated with the responsiveness to corticosteroids. METHODS AND ANALYSIS: The design is a prospective cohort study of 1008 children aged 1-17 years meeting a strict definition of asthma and presenting with a clinical score of ≥4 on the validated Pediatric Respiratory Assessment Measure. All children will receive standardised severity-specific treatment with prednisone/prednisolone and cointerventions (salbutamol with/without ipratropium bromide). Determinants, namely viral aetiology, environmental tobacco smoke and single nucleotide polymorphism, will be objectively documented. The primary efficacy endpoint is the failure of emergency department (ED) management within 72 h of the ED visit. Secondary endpoints include other measures of asthma severity and time to recovery within 7 days of the index visit. The study has 80% power for detecting a risk difference of 7.5% associated with each determinant from a baseline risk of 21%, at an α of 0.05. ETHICS AND DISSEMINATION: Ethical approval has been obtained from all participating institutions. An impaired response to systemic steroids in certain subgroups will challenge the current standard of practice and call for the immediate search for better approaches. A potential host-environment interaction will broaden our understanding of corticosteroid responsiveness in children. Documentation of similar effectiveness of corticosteroids across determinants will provide the needed reassurance regarding current treatment recommendations. RESULTS: Results will be disseminated at international conferences and manuscripts targeted at emergency physicians, paediatricians, geneticists and respirologists. TRIAL REGISTRATION NUMBER: This study is registered at Clinicaltrials.gov (NCT02013076).

Spontaneous spinal epidural hematoma in an 11-month-old girl.

An 11-month-old girl was admitted for a 2-month history of regression of motor milestones and lateralizing neurologic findings. Tests for hypercoagulability were all within normal limits except for a moderately elevated fibrinogen level. Urine and blood cultures were negative for growth. Complete MRI of the spine revealed a well-defined extradural inhomogeneous signal intensity extending from C(4) to T(3) suggestive of a subacute hematoma with evidence of evolving hemorrhagic change. There was no evidence of underlying arterial venous fistula or malformation. She underwent a cervicothoracic laminoplasty and evacuation of the hematoma. The clot was confirmed to be a hematoma on pathologic investigation. She made an uneventful recovery with gradual return of neurologic function. This case represents the longest known duration between initial symptoms and definitive management of spontaneous spinal epidural hematoma.

Psychological features of subjects with idiopathic environmental intolerance.

OBJECTIVES: Idiopathic environmental intolerance (IEI) is associated with unexplained symptoms attributed to non-noxious levels of environmental substances. Clinically, some of the symptoms of IEI overlap with those of panic disorder (PD). We have recently reported a link between IEI and panic responses to a single inhalation of 35% carbon dioxide (CO(2)), a reliable panic induction challenge. This study assessed depression, stress, anxiety, and agoraphobic symptoms among IEI subjects from our previous study versus healthy controls. METHODS: Thirty-six IEI and 37 control subjects with no preexisting psychiatric history were compared on self-report psychological questionnaires. RESULTS: IEI subjects scored significantly higher than controls on the Agoraphobic Cognitions Questionnaire (ACQ), Depression Anxiety Stress Scales (DASS), and Mobility Inventory for Agoraphobia (MI) (Student's t, P<.05). CONCLUSIONS: IEI subjects represent a group with morbidity significantly higher than a control population but less than what would be expected for a clinical psychiatric population.

Idiopathic environmental intolerance: increased prevalence of panic disorder-associated cholecystokinin B receptor allele 7.

BACKGROUND: A growing body of evidence suggests that idiopathic environmental intolerance (IEI) is a psychophysiologic disorder with prominent features of anxiety/panic and somatization, although proponents of a toxicogenic explanation claim, despite a lack of convincing evidence, that symptoms arise from exposure to otherwise nonnoxious environmental agents. Patient behaviour is characterized by strenuous avoidance of perceived triggers to the point of severe impairment of normal social and vocational functioning. IEI proponents claim that previous studies showing a high prevalence of psychopathology in patients with IEI and studies showing panic responses to known panicogenic challenges merely reflect the anxiety-producing result of living with IEI. OBJECTIVE: We explored whether IEI and panic disorder, personality traits, or both shared an underlying neurogenetic basis that would predate the anxiety of IEI symptomatology. The DNA of patients with IEI was examined for the presence of known panic disorder-associated cholecystokinin B (CCK-B) receptor alleles and for personality trait-associated dopamine D4 receptor polymorphisms. METHODS: Eleven patients with typical IEI symptoms were recruited and were individually matched to normal control subjects from an existing bank for age, sex, and ethnic background. Genomic DNA was extracted from peripheral blood samples. CCK-B and dopamine D4 receptor polymorphisms were examined by using standard PCR-based techniques. RESULTS: There was a significantly higher prevalence of the panic disorder-associated CCK-B receptor allele 7 in subjects with IEI (9/22 [40.9%]) compared with control subjects (2/22 [9.1%], P =.037). There was no difference in personality trait-associated polymorphisms of the gene encoding dopamine D4 receptor between patients and control subjects. CONCLUSIONS: These findings provide preliminary evidence that IEI and panic disorder share a common neurogenetic basis, which would predate the anxiety-producing effects of IEI symptoms. Further studies with larger samples are warranted, but these results support previous studies that suggest that panic disorder may account for much of the symptomatology in at least some cases of IEI and provide a basis for rational treatment strategies.

Prevalence and causes of cough in chronic dialysis patients: a comparison between hemodialysis and peritoneal dialysis patients.

Peritoneal dialysis (PD) and hemodialysis (HD) are both common forms of dialysis for patients with end-stage renal disease. A few case reports have suggested that cough is associated with PD. From 1991 to 1998, 17 patients being treated with PD at the Toronto Western Hospital demonstrated persistent cough severe enough for referral to a respirologist. Causes of cough, often more than one cause per patient, included asthma, post-nasal drip, gastroesophageal reflux disease (GERD), chronic obstructive pulmonary disease, congestive heart failure, allergic rhinitis, pleural effusion, and respiratory infection. The aim of this cross-sectional study was to establish the prevalence of cough among PD patients, to determine if PD patients more commonly have a dry persistent cough than do HD patients, and, if the latter case is true, the possible reasons for it. A detailed survey of 92 PD patients and 91 HD patients was conducted in 1998 and 1999 at the University Health Network. Survey questions inquired about patient respiratory symptoms since onset of dialysis. Charts were reviewed to obtain information on use of medications possibly relevant to cough. In the PD and HD groups, 52% and 23% were females (p = 0.001), and the mean ages were 59.1 and 60.1 years, respectively. Angiotensin converting enzyme (ACE) inhibitors had been taken by 65% (PD) and 55% (HD) of patients, and beta-blocking medications by 43% (PD) and 51% (HD). Since initiation of dialysis--mean 2.7 years (PD) and 3.7 years (HD)--22% of PD patients reported persistent cough versus 7% of HD patients (p = 0.003). Although no significant association was seen between cough and self-reported heartburn in HD patients (p = 0.439), a significant association between cough and self-reported heartburn was seen in PD patients: 67% of PD patients with persistent cough reported heartburn versus 29% of those without cough (p = 0.008). The findings suggest that GERD and associated cough are more common in PD patients than in HD patients, perhaps owing to increases in intra-abdominal pressure from the peritoneal dialysate.

Carbon dioxide inhalation challenges in idiopathic environmental intolerance.

BACKGROUND: Idiopathic environmental intolerance (IEI) is associated with unexplained physical symptoms, which overlap considerably with those of panic disorder (PD). OBJECTIVE: This study tested the hypothesis that patients with symptoms to suggest IEI exhibit features of PD in response to nonnoxious environmental stimuli. METHODS: A single-blind, case-control 35% carbon dioxide inhalation challenge was conducted at a university-based occupational health unit with the use of standardized psychologic questionnaires involving 36 patients with IEI and 37 healthy control subjects. The main outcome measures included panic attack symptoms and scores on the Anxiety Sensitivity Index, a measure of panic-related anxiety. RESULTS: Patients with IEI scored significantly higher on the Anxiety Sensitivity Index than control subjects did (P <.05). Significantly more patients with IEI (71%) than control subjects (26%) fulfilled panic attack criteria after carbon dioxide (P <.001). Physiologic responses to the challenge were not significantly different between groups. CONCLUSIONS: Results suggest that, similar to patients with PD, patients with IEI display high anxiety sensitivity and in response to carbon dioxide inhalation tend to experience heightened anxiety and panic attacks.