Edward J. O'Connell

Exposure to an Aeroallergen as a Possible Precipitating Factor in Respiratory Arrest in Young Patients with Asthma

BACKGROUND Exposure to airborne spores of the common mold Alternaria alternata has been implicated in asthma attacks. Such exposure is particularly frequent in the Midwest during the summer and fall months. To determine the role of A. alternata in triggering severe asthma attacks, we investigated the cases of 11 patients with asthma who had sudden respiratory arrest and determined the frequency of sensitivity to this allergen in these patients. METHODS The 11 patients (age range, 11 to 25 years) with initial episodes of respiratory arrest, which was fatal in 2 patients, were identified in the course of their care in our pediatric and adult clinical allergy practice and by a retrospective review of all Mayo Clinic records of patients with severe asthma cared for between 1980 and 1989. Skin-test reactivity to A. alternata and levels of IgE antibody against this mold in the 11 patients were compared with those in 99 matched controls with asthma who had no history of respiratory arrest. RESULTS All the patients came from the upper Midwest, and the episodes of respiratory arrest occurred in the summer or early fall. Ten of the 11 patients with asthma who had respiratory arrest (91 percent) had positive skin-puncture tests for sensitivity to alternaria, as compared with 31 percent of the controls (P less than 0.001), and the serum levels of IgE antibodies to alternaria were elevated in all 9 patients tested. Among the covariates we examined (age, sex, and distance from the Mayo Clinic), only age was a significant confounder. After adjustment for age, alternaria skin-test reactivity was found to be associated with an increase of approximately 200-fold in the risk of respiratory arrest (adjusted odds ratio, 189.5; 95 percent confidence interval, 6.5 to 5535.8). CONCLUSIONS Exposure to the aeroallergen A. alternata is a risk factor for respiratory arrest in children and young adults with asthma.

Hypothalamic-pituitary-adrenal axis suppression after short-term, high-dose glucocorticoid therapy in children with asthma

Short-term, high-dose oral glucocorticoid therapy is often required for control of acute asthma episodes in children. To evaluate possible hypothalamic-pituitary-adrenal (HPA) axis suppression after such therapy, we studied 11 children with just asymptomatic asthma before and at 3 and 10 days after completion of a five-day course of prednisone (up to 2 mg/kg/day in divided doses, maximum dose = 60 mg/day). HPA axis responsiveness was tested by measuring plasma corticosteroid levels before and after insulin-induced hypoglycemia. When these levels were compared to pretreatment levels, there was a statistically significant blunting of the peak corticosteroid responses to hypoglycemia 3 days after completion of the course of prednisone (p less than 0.001). However, corticosteroid responses were normal in all children 10 days after completion of the course of prednisone. We concluded that a single course of short-term, high-dose glucocorticoid therapy in children with asymptomatic asthma produces only transient (less than 10 days) HPA axis suppression.

Interobserver variability in medical record review: An epidemiological study of asthma

Interobserver variability during the data collection for a large retrospective study of asthma was assessed. After extensive training by three physician investigators, two nurses collected study data from existing medical records using an explicit protocol. At four time intervals, samples of records already abstracted by one nurse were reviewed and re-abstracted by another nurse assigned to the project. The unweighted kappa coefficient was used to evaluate observer reliability. Most of the kappa coefficients were > or = 0.6, suggesting good to excellent agreement. Agreement was highest for demographic, clinical and medication variables, while judgement variables had the lowest kappa coefficients. The well known dependence of kappa on the prevalence of the variable studied was evident in these data. We strongly recommend periodic monitoring of observer reliability in any study using more than one individual to collect data to ensure reliable data collection.

Functional Respiratory Disorders

LEARNING OBJECTIVES Reading this article will enable health care providers to recognize and to diagnose paroxysmal sneezing, sighing dyspnea, habit cough, and vocal cord dysfunction and to reinforce their knowledge of the epidemiology, etiopathology, clinical features, and treatment of these disorders. DATA SOURCES The literature was reviewed using a MEDLINE search for information relating to the above-mentioned disorders. Indexing terms used included psychogenic wheezing, vocal cord dysfunction, functional respiratory disorders, sighing dyspnea, paroxysmal sneezing, habit cough, and psychogenic stridor. Review was restricted to English language articles from 1966 onward, with cross-referencing to obtain older references. STUDY SELECTION All human studies that clearly identified the above-mentioned disorders as being nonorganic on the basis of historic and appropriate laboratory evaluation were reviewed. No studies were rejected on the basis of subject age, although special emphasis was given to articles concerning children and adolescents (<18 years old). Of all initially identified studies, 95% fulfilled the inclusion criteria. RESULTS Functional respiratory disorders are common and affect mostly children, adolescents, and young adults, resulting in considerable morbidity and contributing significantly to patient and physician cost and frustration. A history of a psychiatric disorder with temporally related psychogenic stressors is frequently found. Professionals disagree on the technical classification of some of these conditions (ie, psychosomatic versus somatoform), but there is agreement that treatment directed toward underlying stressors should be the cornerstone of therapy. CONCLUSIONS Functional respiratory disorders must be considered in patients with atypical symptoms, especially those resistant to conventional therapy. Possible psychogenic stressors must be inquired into and, when identified, treated in a multidisciplinary manner. This may involve reassurance regarding the absence of significant organic abnormality, counseling, and occasional recourse to formal psychiatric intervention.

Nebulized lidocaine in the treatment of severe asthma in children: a pilot study

BACKGROUND Glucocorticoids have been used to treat asthma since the 1950s; however, their adverse systemic effects have limited their duration of use and dosage. Unfortunately, many patients with severe asthma often require oral glucocorticoids in addition to inhaled glucocorticoids. Alternatives to glucocorticoids have been sought with mixed success. Recently, lidocaine has been added to the list of potent glucocorticoid sparing agents for the treatment of severe asthma. OBJECTIVE We report the first group of pediatric patients with severe asthma treated with nebulized lidocaine. METHODS The study was performed in an open manner with 6 severely asthmatic patients followed in the Pediatric Allergy and Immunology Section, Mayo Clinic. The only intervention was the institution of nebulized lidocaine (0.8 mg/kg/dose to 2.5 mg/kg/dose t.i.d to q.i.d). The average daily steroid requirement was followed during the administration of the nebulized lidocaine. RESULTS During a mean of 11.2 months of therapy (range 7 to 16 months) 5 of the 6 patients completely discontinued their oral glucocorticoids within an average time of 3.4 months (range 1 to 7 months). CONCLUSIONS After further study, lidocaine may prove to be the first non-toxic, steroid alternative to patients with severe steroid-dependent asthma.

Pediatric allergy: a brief review of risk factors associated with developing allergic disease in childhood

OBJECTIVE To briefly review some of the factors that have been implicated in the causation of the increased prevalence of allergic disease in children. DATA SOURCES MEDLINE search of original research and review articles related to the various risk factors considered responsible for the increased prevalence of allergic disease in children. STUDY SELECTION Author selected references. CONCLUSIONS It has been established that there is an increased prevalence of allergic disease, especially in children. Risk factors that are currently under investigation include: genetic atopic predisposition, early childhood allergen exposure and sensitization, occurrence of viral respiratory infections in young children, maternal smoking during pregnancy, poor dietary factors, lack of breast-feeding, childhood obesity, having a certain immunologic predisposition (Th2-prone), air pollution, and frequent immunizations in childhood. It is most likely that the occurrence of allergic disease will be found to be multifactorial.

Familial interstitial lung disease in children: Response to chloroquine treatment in one sibling with desquamative interstitial pneumonitis

We describe a male infant with biopsy‐confirmed interstitial lung disease (ILD) who responded to chloroquine, after he failed to improve on oral corticosteroids or cyclophosphamide. The infant presented at 8 days of age with respiratory distress and cyanosis. Lung biopsy at 8 weeks of age was consistent with desquamative interstitial pneumonitis (DIP). He was treated with corticosteroids at 2 weeks of age because of a family history of two siblings who died during infancy and who had DIP on postmortem examination. At 8.5 months, our patient was treated with cyclophosphamide because of lack of response to corticosteroids therapy. At 14 months of age, he began treatment with chloroquine in addition to corticosteroids and had a dramatic response within 3 weeks. The patient has been maintained successfully on continuous treatment with chloroquine alone for more than 9 years since this treatment was started. Pediatr. Pulmonol. 1997; 23:55–61.

Review of the unique properties of budesonide

BACKGROUND The aim of inhaled corticosteroid (ICS) therapy for asthma is to attain high therapeutic activity in the airways while keeping the risk of systemic adverse effects relatively low. However, the physicochemical and pharmacokinetic properties of various ICSs affect this ratio, thereby influencing their ability to fulfill the requirements of an ideal agent. OBJECTIVE This article reviews the physical and pharmacokinetic properties of budesonide, outlining how they, safety data, and use of different inhalation devices enable budesonide to meet many of the clinical requirements of an ideal ICS for the treatment of asthma. RESULTS ICS efficacy is influenced by lipophilicity, lung deposition, and retention in airway tissue, whereas the rate of elimination determines systemic activity. Budesonide is retained in the airways to a greater extent than other ICSs because of an esterification process that increases its lipophilicity. The prolonged retention of budesonide in the airways may contribute to its efficacy when administered QD. In addition to a pressurized metered-dose inhaler, budesonide is available as a dry-powder inhaler and in nebulized form, which can be used by asthma patients aged > or =6 months. CONCLUSIONS When combined with delivery devices suitable for a spectrum of patient groups, the physical and pharmacokinetic properties of budesonide lend it many of the characteristics of an ideal ICS, including favorable efficacy and tolerability profiles.

Serum IgG4 concentrations and allergen-specific IgG4 antibodies compared in adults and children with asthma and nonallergic subjects

We describe the development of specific immunoassays for IgG4 protein and for allergen-specific IgG4 antibodies. We also measured the concentrations of IgG4 protein and determined the frequencies of detectable IgG4 antibodies to several common allergens in sera from adults and children with asthma and from nonallergic subjects. Serum concentrations of IgG4 protein increase with age but are not different in children with asthma and nonallergic children, nor does a raised serum concentration predict a severe clinical course in childhood asthma. IgG4 antibodies to milk and egg are common in children and adults and are more common in children with asthma than in nonallergic children less than 3 years of age. The presence of detectable IgG4 antibodies or a raised concentration of IgG4 protein in serum is not useful empirically as a diagnostic indicator of asthma but more likely results from antigen exposure occurring at mucosal surfaces.

Aspirin-induced asthma in children

The case histories of five children with well-documented aspirin-induced asthma attacks are presented. Four of the children differed in several respects from the aspirin-sensitive adult. These sensitive children appeared to have a lower incidence of nasal polyposis and a higher incidence of atopic constitutions. Affected patients must be educated to avoid not only plain aspirin but also aspirin-containing combination drugs. Concomitant intolerance to certain aniline dye-derived coloring agents also should be suspected.