T cell subsets, epitope mapping, and HLA-restriction in patients with allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease characterized by Aspergillus fumigatus (Af) colonization, IgE and IgG anti-Af antibodies, pulmonary infiltrates, bronchiectasis, and pulmonary fibrosis. Little is known regarding T cell responses and their role in the pathogenesis of ABPA. To examine T cell reactivity to Af antigens, T cell clones (TCC) specific to the Asp f 1 antigen, an 18-kD protein of Af, were established from the peripheral blood of three ABPA patients. The majority of TCC isolated from ABPA patients, and specific for the Asp f 1 allergen of Af, are IL-4 producing CD4+ cells of the Th2 phenotype. Further analysis in this study revealed that the majority of TCC reacted to mainly two epitopes of Asp f 1, while the remaining TCC reacted to three additional "minor" epitopes. Blocking studies using monoclonal antibodies specific for class II HLA-D region gene products showed that most TCC, 19/21, were restricted by HLA-DR molecules, and the remaining two clones by HLA-DP molecules. The use of a panel of HLA-matched and mismatched EBV-transformed B cells as antigen presenting cells revealed that the HLA-DR restriction was mediated exclusively by either the HLA-DR2 or HLA-DR5 alleles. Genotyping of DRB1 gene products showed that class II presentation for most clones was not restricted to a single allele, representing DRB1 gene products of either HLA-DR2 or DR5. These studies offer insight into the cellular and molecular determinants which contribute to the immunopathophysiology of ABPA.

The Jewish Hospital of St Louis Therapeutic Grand Rounds No. 14. Hypersensitivity pneumonitis.

Two examples of immunologically mediated diseases of the lung have been discussed. The first, extrinsic allergic alveolitis, is caused by sensitivity to inhalation of an organic dust. It is largely a restrictive type of lung disease and is probably caused by a combination of type 3 and type 4 allergic reactions. The second disease, allergic bronchopulmonary aspergillosis, is caused by a type 1 and type 3 allergic response to Aspergillus antigen in a basically atopic, generally asthmatic individual. It is vital to keep the diagnostic index of suspicion high so as to recognize these diseases early enough to prevent irreparable tissue damage. Extrinsic allergic alveolitis may masquerade as idopathic pulmonary fibrosis or Hamman-Rich syndrome. Allergic aspergillosis may be called Loeffler pneumonia or PIE syndrome (pulmonary infiltrates with eosiniphilia). Failure to diagnose properly may result in extensive pulmonary fibrosis or bronchiectasis and condemn the patient to a lifetime as a pulmonary cripple.

A fatal case of theophylline intoxication.

A fatal case of theophylline intoxication is presented in which a number of factors leading to a decrease in theophylline clearance and the patient's death were possibly operative. These included advanced age, chronic lung disease, liver disease, and administration of cimetidine. Since early symptoms of the toxic effects of theophylline can mimic peptic ulcer disease, cimetidine might be prescribed for the gastrointestinal symptoms with subsequent worsening of theophylline poisoning. Theophylline plasma concentration should be determined whenever drugs affecting theophylline clearance are administered simultaneously.

Passive smoking. Effects on bronchial asthma.

Ten patients with bronchial asthma and ten control subjects were exposed to sidestream cigarette smoke (passive smoking) for one hour in an environmental chamber. All subjects showed the same increase in carboxyhemoglobin as a result of the exposure: 0.40 percent. The asthmatic group demonstrated a significant linear decrease in pulmonary function during this exposure. After one hour of smoke, FEV1 decreased 21.4 percent, FEF25-75% decreased 19.2 percent, and FVC decreased 20.0 percent in the asthmatic patients. These alterations were readily reversible in all subjects when given inhalations of metaproterenol following the exposure. The control subjects showed no change in pulmonary function when exposed to identical conditions. These data show that nonsmokers with bronchial asthma are at risk when exposed to sidestream cigarette smoke in an environmental chamber.

A 12-year longitudinal study of Aspergillus sensitivity in patients with cystic fibrosis.

STUDY OBJECTIVE: The object of the study was to longitudinally follow immune parameters of Aspergillus fumigatus sensitization so as to predict those at risk for developing allergic bronchopulmonary aspergillosis (ABPA). DESIGN: Patients were evaluated for 5 immune parameters (skin test [ST], positive precipitating antibody [PPN], total IgE, IgE anti-A fumigatus antibody [IgE-Af], and IgG anti-A fumigatus antibody [IgG-Af]) at yearly intervals over a 12-year time period. SETTING: Patients were enrolled and evaluated during routine visits to the cystic fibrosis (CF) clinic at Cardinal Glennon Children's Hospital, St. Louis. PATIENTS: One hundred eighteen patients with documented CF participated. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Six patients were diagnosed as having ABPA. In the non-ABPA patient group, 42% had a positive ST, 42% were PPN positive, 54% had IgE-Af, 61% had IgG-Af, and 10% had an IgE greater than 1,000 IU/mL at some point in time. However, on follow-up, 18% lost skin reactivity, 54% lost-PPN, 53% lost IgE-Af, 45% lost IgG-Af, and IgE greater than 1,000 IU/mL declined more than 72% in 64% of patients. These losses were spontaneous, without systemic corticosteroid intervention. CONCLUSIONS: Spontaneous diminution and loss of immune parameters in non-ABPA CF patients prevented us from defining a profile of sensitivity likely to result in ABPA. This variability highlights the importance of obtaining follow-up studies and including clinical symptoms when considering the diagnosis of ABPA in patients with CF.

Effects of hemodialysis on theophylline kinetics.

Difficulties encountered in controlling theophylline blood concentrations in an asthmatic patient on hemodialysis prompted us to study the effect of hemodialysis on theophylline kinetics. Plasma theophylline extraction ratios, clearances, and half-lives were determined during dialysis for 11 adults given an intravenous infusion of 4 mg/kg aminophylline. For comparison, eight of these patients were evaluated for theophylline half-lives when not dialyzed. Extraction ratios of theophylline during dialysis ranged from 0.22 to 0.51 (0.35 +/- 0.08) for these patients, indicating that a mean of 36 per cent plasma theophylline was removed during each pass through the dialyzer. This compares with a mean extraction ratio of urea of 0.63 +/- 0.07. Plasma clearance of theophylline during dialysis ranged from 52 to 124 ml/min (83 +/ 20 ml/min). Plasma theophylline half-lives during dialysis ranged from 1.6 to 3.4 hours (2.3 +/- 0.5 hours). Theophylline half-lives when not on dialysis ranged from 3.5 to 8.2 hours (5.0 +/- 1.7). Theophylline clearance was significantly faster in every patient during dialysis. Asthmatics requiring hemodialysis should receive additional theophylline during dialysis if therapeutic blood levels are to be maintained. Routine hemodialysis will significantly increase clearance in a toxic patient in whom life-threatening toxicity is occurring and charcoal hemoperfusion is unavailable.

Sinusitis in the aged. Optimal management strategies.

Sinusitis is a common medical condition in the elderly; however, the clinical presentation is often subtle and the condition may not be readily diagnosed. The most important clinical clue to the diagnosis of acute sinusitis is the continuation of symptoms after a typical cold has subsided. In chronic sinusitis there is often a distinct lack of symptoms, although most patients will have nasal obstruction and purulent post-nasal drip. On physical examination, the patient with sinusitis will have thick, purulent, green or deep yellow secretions in the nasal passages. The use of radiographic imaging, such as sinus roentgenograms or CT scans, will help confirm the diagnosis. The goal of treatment of sinusitis is eradication of infection with clearance of the infected material from the sinuses. While the use of an appropriate antibiotic is necessary, the use of ancillary therapy is also of utmost importance. Steam and nasal saline, decongestants, topical corticosteroids and mucoevacuants are given in an attempt to reduce nasal obstruction, increase sinus ostia size, promote improved mucociliary function, decrease mucosal inflammation and thin secretions. In selected patients who fail to respond to aggressive medical therapy, functional endoscopic surgery can often provide relief. In patients with poorly controlled asthma, treatment of underlying sinusitis has been shown to dramatically improve the asthmatic state.

Sphenoethmoidectomy: its role in the asthmatic patient.

Fifty patients who underwent intranasal sphenoethmoidectomy at the St Louis University Medical Center between July 1977 and April 1980 have been evaluated with respect to preoperative extent of disease and medication requirement as well as postoperative course and reduction in medication requirements, if any. These patients were followed jointly by the Departments of Allergy and Otolaryngology. Most of these patients were not allergic, and over half had intrinsic asthma. Fifteen of the 50 patients, all asthmatic, gave a history of aspirin sensitivity. Many had had previous nasal surgical treatment for polyps. Patients on large corticosteroid dosages had long-lasting reductions or elimination of their corticosteroid requirements in most cases. Similarly, most patients had long-lasting nasal airway improvement and reduction or elimination of recurring sinusitis. Antibiotics and antihistamine-decongestant preparations were sharply diminished in these patients. Although aspirin sensitivity was associated with some of the more severe asthmatic patients, it appeared not to be a factor in the responses to surgical treatment.

Immunologically mediated lung diseases. Extrinsic allergic alveolitis and allergic bronchopulmonary aspergillosis.

Early recognition and treatment of immunologically mediated diseases of the lung are vital to prevent irreparable damage. Extrinsic allergic alveolitis and allergic bronchopulmonary aspergillosis are often confused but should not be difficult to distinguish. The former is nonatopic and is marked by chills, fever, chest pains, cough, dyspnea, and restrictive pulmonary function. The immunologic hallmark is the presence of precipitating antibody to the suspected antigen. Allergic bronchopulmonary aspergillosis is atopic and is marked by low-grade fever, obstructive pulmonary function, markedly elevated serum IgE levels, and positive immediate and late response on skin tests. Both diseases respond well to early corticosteroid therapy. Prophylactic measures are also important in controlling extrinsic allergic alveolitis.