Biomedical subjects

Joseph D Spahn

Publications and source records attributed to Joseph D Spahn.

25 records · Page 2Linked to original sources

PubMed2003

Treating the wheezing infant.

The management of infants and small children with asthma is a challenging task because of the many issues unique to this age group that deserve special consideration. The diagnosis of asthma is limited by inherent difficulties in obtaining objective measures of lung function and airway inflammation. In persistently symptomatic patients, the decision to initiate controller therapy is not as great an issue as it is in infants and young children with recurrent episodic wheeze in whom early intervention may allow a window of opportunity potentially to alter the course of the disease. The reality is that even if atopy has been consistently implicated in the development of persistent asthma, there is not a well-established set of criteria by which patients who are likely to benefit from early intervention controller therapy can be identified. Hence, large prospective studies need to be performed evaluating the impact of early pharmacologic intervention on the natural history of infantile asthma. Many areas needing investigation involve what medications to use, how best to deliver the medications, and how to monitor the response to treatment. Only a few medications have been approved for use in this population. Long-term studies evaluating available drugs such as inhaled glucocorticoids, LABAs, and the leukotriene-modifying agents in young children still need to be performed.

Administration, Inhalation↗

PubMed2003

Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma.

OBJECTIVE: Exhaled nitric oxide (FE(NO)) was evaluated in children with asthma after 4 to 6 years of treatment with budesonide, nedocromil, or albuterol as needed. STUDY DESIGN: FE(NO), spirometry, total eosinophil count, and serum eosinophil cationic protein levels were obtained from 118 children at the Denver site of the Childhood Asthma Management Program upon completion of treatment and after a 2- to 4-month washout. RESULTS: Budesonide-treated patients had significantly lower median (1st, 3rd quartile) FE(NO) (21.5 [13.2, 84.4] vs 62.5 [26.2, 115.0] ppb, P <.01) and eosinophil cationic protein levels (17.4 [10.1, 24.3] vs 24.0 [15.4, 33.9] mg/dL, P =.05) compared with placebo, whereas no differences were noted between nedocromil and placebo groups. After washout, FE(NO) levels were similar between the three treatments. FE(NO) levels significantly correlated with degree of bronchial hyperresponsiveness, bronchodilator reversibility, allergen skin prick tests, serum IgE, and total eosinophil count. FE(NO) levels were also higher in patients with nocturnal symptoms and in patients requiring beta-agonist use at least once weekly. CONCLUSIONS: Budesonide therapy was more effective than nedocromil in reducing FE(NO). Unfortunately, the effects of long-term budesonide were not sustained after its discontinuation. FE(NO) may be a complementary tool to current practice guidelines in assessing asthma control and medication response.

Anti-Asthmatic Agents↗

PubMed2003

Histopathology of severe childhood asthma: a case series.

BACKGROUND: To date, little has been published describing the pathology of severe childhood asthma. The currently accepted model of asthma holds that persistent airway inflammation leads to various symptoms of asthma, airway hyperresponsiveness, and airway remodeling that ultimately results in permanent loss of lung function. METHODS: Evaluation of six children referred to the National Jewish Medical and Research Center with difficult-to-control asthma, despite aggressive anti-inflammatory therapy, who underwent bronchoscopy with endobronchial biopsy to better characterize their disease. RESULTS: In every case, endobronchial biopsies revealed changes consistent with airway remodeling characterized by thickening of the basement membrane, smooth-muscle hypertrophy, with varying degrees of goblet-cell and submucous gland hyperplasia. The degree of subbasement membrane thickening did not appear to correlate with baseline FEV(1), ultimate FEV(1) following aggressive therapy, or lability in lung function. In five of six cases, there was minimal to no histologic evidence for airway inflammation with mild and patchy submucosal lymphocytic infiltration noted; eosinophils and neutrophils were not present. Further, the majority of the patients achieved normal FEV(1) values despite significant subbasement membrane thickening, counter to the current beliefs regarding airway remodeling and irreversible loss of lung function. CONCLUSIONS: This case report highlights some of the shortcomings of the current inflammatory paradigm for severe asthma. Despite little evidence of ongoing airway inflammation, many of the subjects displayed significant lung function lability. The lack of inflammation argues against steroid resistance at a cellular level, although it could be argued that inflammation may have been distal to the site sampled. Additionally, normal to nearly normal lung function was achieved despite the presence of significant remodeling. These findings suggest the need to look beyond inflammation to fully treat severe asthma and ultimately alter its progression.

Adolescent↗

PubMed2003

A comparison of the clinical characteristics of children and adults with severe asthma.

OBJECTIVES: This study sought to better define the clinical characteristics of severe asthma in both children and adults, and to evaluate the effect of asthma duration on multiple parameters of disease severity. DESIGN: Retrospective analysis of prospectively collected data on 275 patients (125 children) with severe asthma who were admitted to a tertiary asthma referral center. METHODS: Demographics, lung function (ie, spirometry and body box plethysmography), glucocorticoid (GC) pharmacokinetic studies, and lymphocyte stimulation assays were performed on all patients. RESULTS: Children were as likely to require therapy with high-dose inhaled GCs and long-term therapy with oral GCs, and to have had a prior intubation, yet they had significantly less airflow limitation (mean [+/- SEM] FEV(1), 74.0 +/- 2.1% predicted vs 57.1 +/- 1.8% predicted, respectively; p < 0.0001), less resistance to airflow (mean airway resistance, 140.3 +/- 8.5% predicted vs 311 +/- 18% predicted, respectively; p < 0.0001), and larger lung volumes (mean total lung capacity, 116.4 +/- 1.6% predicted vs 105.3 +/- 1.8% predicted, respectively; p < 0.0001) compared to adults. Children were more likely to be male and to display greater responsiveness to GCs in vitro. Lung function impairment was associated with asthma duration in children and in adults with onset of asthma in childhood, while there was no relationship between disease severity and asthma duration among those with adult-onset asthma. Despite significant differences in disease duration, patients with adult-onset asthma had equally compromised lung function compared to adults with long-standing asthma. CONCLUSIONS: Children with severe asthma tended to be male, to have less severe airflow obstruction, and to display greater responsiveness to GCs in vitro compared to adults. Symptoms and episodic acute declines in lung function may precede chronic airflow limitation in this group of children. As such, it may be more relevant to follow the deterioration in lung function over time in children. Finally, disease severity in children and adults whose onset of asthma occurred in childhood was related to disease duration, but not in patients with onset of asthma in adulthood.

Adolescent↗

PubMed2002

Steroid-unresponsive asthma.

Although most patients with chronic asthma respond to corticosteroid therapy, a small subset of asthmatics are unresponsive to corticosteroids and demonstrate persistent airway obstruction and inflammation despite treatment with high doses of systemic glucocorticoids. There are at least two types of steroid-resistant asthma. Type I steroid-resistant (SR) asthma is cytokine induced and is associated with increased expression of glucocorticoid receptor beta, a less active glucocorticoid receptor isoform. Type II SR asthma is due to low numbers of glucocorticoid receptors. An important distinction between these two types of SR asthma is that the glucocorticoid receptor defect in Type I, but not Type II, SR asthma is reversible in culture and is sustained by incubation with combination interleukin (IL)-2 and IL-4. The treatment of these patients requires a systematic approach to rule out underlying conditions that lead to steroid resistance or treatment failure as well as the use of alternative strategies to inhibit airway inflammation.

Journal Article↗

PubMed2002

Inhaled steroids: are they all created equal?

New inhaled steroids or new formulations of inhaled steroids continue to be introduced on a regular basis in an attempt to replace hydrochlorofluorocarbon propellant-based, pressurized, metered dose delivery systems. New delivery systems are being introduced with either a replacement propellant in a pressurized metered dose inhaler, such as a hydrofluoroalkane, or a dry powder, breath-actuated delivery device. Although there are now many different steroid preparations and delivery devices available, little is known about their relative beneficial and adverse effects. Several recent studies have introduced methods to determine the comparative efficacy of different inhaled steroids as related to a standardized measure of systemic effect. Physicians should be familiar with the differences among the available choices of inhaled steroid-delivery device combinations in order to select therapy that will optimize response and minimize the risk for adverse effects.

Journal Article↗

PubMed2002

Childhood asthma: new insights into management.

Recently, a concerted effort has been made to reverse the trend of increasing asthma mortality and morbidity. One additional strategy might be to recognize patients at risk for persistent asthma and to intervene early. This review summarizes new information on asthma pathogenesis that has helped shape a new direction in managing childhood asthma. At the core is the recognition that asthma is a chronic inflammatory disease. Subsequently, inhaled steroids, the most potent anti-inflammatory asthma medications, have emerged as the cornerstone of the management of persistent asthma. The recent report of the National Heart, Lung, and Blood Institute's Childhood Asthma Management Program provides a comprehensive "profile of performance" for 3 treatment choices for the management of persistent asthma. This study answers questions regarding the benefits and shortcomings of the medications evaluated and prompts a closer evaluation of the long-term effects of other treatment strategies, including medications currently being developed. Although intervention with inhaled steroids offers new opportunities to control the development of asthma, one must be cognizant of potential risks in early and long-term therapeutic intervention. This review provides a perspective on our present knowledge, the rationale for early intervention, and opportunities for more aggressive therapy, as well as speculation on how ongoing clinical research will continue to play a role in advancing asthma care and moving toward a "cure" for this life-threatening disease.

Adrenal Cortex Hormones↗