Lung-resident CD4⁺ T cells are sufficient for IL-4Rα-dependent recall immunity to Nippostrongylus brasiliensis infection.

Immunity to Nippostrongylus brasiliensis reinfection requires pulmonary CD4⁺ T-cell responses. We examined whether secondary lymphoid recruited or pre-existing lung CD4⁺ T-cell populations coordinated this immunity. To do this, we blocked T-cell egress from lymph nodes using Fingolimod (FTY720). This impaired host ability to resolve a primary infection but did not change effectiveness of recall immunity. Associated with this effective recall immunity was the expansion and T helper type 2 polarization of a pre-existing pulmonary CD4⁺ T-cell population. LTßR-Ig (lymphotoxin beta-receptor fusion protein)-mediated disruption of stromal cell organization of immune cells did not disrupt this recall immunity, suggesting that protection was mediated by a pulmonary interstitial residing CD4⁺ T-cell population. Adoptive transfer of N. brasiliensis-experienced pulmonary CD4⁺ T cells from FTY720-treated wild-type or T-cell interleukin (IL)-4Rα-deficient mice demonstrated protection to be IL-4Rα dependent. These results show that pre-existing CD4⁺ T cells can drive effective recall immunity to N. brasiliensis infection independently of T-cell recruitment from secondary lymphoid organs.

Identification of clinically relevant cross-sensitization between Soliadgo virgaurea (goldenrod) and Hevea brasiliensis (natural rubber latex).

BACKGROUND: Solidago virgaurea (goldenrod) is a perennial weed from which no allergens have been identified. A high latex content in its leaves has been reported. Although not an airborne allergen, it may be an important occupational sensitizer. OBJECTIVE: To identify allergenic proteins in goldenrod and to determine whether they cross-react with Hevea brasiliensis latex. METHODS: Potential cross-reactive allergens in latex and goldenrod were investigated by immunoblot inhibition and ImmunoCAP inhibition analyses using serum from patients with clinically evident goldenrod and/or latex allergy. Cross reactivity between latex allergens and goldenrod proteins was studied using recombinant Hev b 1, 3, 4, 5, 6.01, 6.02, 8, 9, or 11 in ImmunoCAP inhibition analyses. RESULTS: Immunoglobulin (Ig) E antibodies from individuals with goldenrod allergy bound extracted goldenrod proteins ranging from 20 kDa to 130 kDa in Western blots. Evidence for latex and goldenrod cross reactivity was identified by ImmunoCAP and immunoblot inhibition experiments using serum from patients with strongly positive concomitant latex and goldenrod-specific IgE antibody responses. Observed latex-goldenrod cross reactivity could not be ascribed to any of the recombinant major latex allergens evaluated. CONCLUSIONS: H brasiliensis latex and goldenrod contain cross-reactive and unique allergenic proteins. Exposure to goldenrod may sensitize patients to latex and vice versa.

Patterns of asthma mortality in Philadelphia from 1969 to 1991.

BACKGROUND: The rate of mortality from asthma has increased substantially in the United States since 1978. We analyzed the patterns of the rates of death from asthma in Philadelphia between 1969 and 1991. METHODS: The rates of death from asthma were analyzed and compared with trends in the concentrations of major air pollutants: ozone, carbon monoxide, nitrogen dioxide, particulate matter (particles < 10 microns in diameter), and sulfur dioxide. Univariate and multivariate analyses were used to study the rates of death from asthma from 1985 to 1991 and their association with race, poverty, sex, and other factors. RESULTS: The rate of death from asthma decreased from 1.68 per 100,000 people in 1969 to 0.68 per 100,000 in 1977, but then increased to 0.92 per 100,000 in 1978 and 2.41 per 100,000 in 1991. Between 1965 and 1990, the concentrations of major air pollutants declined substantially. From 1985 to 1991, 258 people were identified for whom asthma was the primary cause of death. According to multivariate analysis, the rates of death from asthma from 1985 to 1991 were significantly higher in census tracts with higher percentages of blacks (P = 0.032), Hispanics (P = 0.013), female residents (P < 0.001), and people with incomes in the poverty range (P < 0.001). CONCLUSIONS: The rates of death from asthma have increased in Philadelphia, whereas concentrations of major air pollutants have declined. The rates are highest in census tracts with the highest percentages of poor people and minority residents, particularly blacks. Public health efforts should target urban areas where the risk of death from asthma is highest.

Comparative study of the safety and efficacy of clarithromycin and amoxicillin-clavulanate in the treatment of acute otitis media in children.

The safety and efficacy of clarithromycin was compared with those of amoxicillin-potassium calvulanate for the treatment of acute otitis media in children. In a multicenter, randomized, investigator-blinded trial, 180 patients (6 months to 12 years of age) with acute otitis media were allocated to receive either clarithromycin, 15 mg/kg in two divided doses (n = 90), or amoxicillin-clavulanate, 40 mg/kg in three divided doses (n = 90), for 10 days. Middle ear samples were obtained by tympanocentesis from 175 of 180 patients. Pathogens were isolated from 137 samples (76%). Eighty-six patients in each treatment group were considered for efficacy analysis. Clinical cure or improvement was achieved within 4 days after treatment in 80 (93%) of 86 patients receiving clarithromycin and in 82 (95%) of 86 patients receiving amoxicillin-clavulanate. Recurrence of infection was observed between 5 and 35 days after treatment in 9 (11%) of 80 patients in the clarithromycin group and in 8 (10%) of 82 patients in the amoxicillin-clavulanate group. Middle ear effusion was found with similar frequency at the end of therapy and at follow-up visits in both treatment groups. Mild gastrointestinal signs and symptoms, the most common side effects, were noted in 20% and 52% of patients in the clarithromycin group and the amoxicillin-clavulanate group, respectively (p < 0.001). We conclude that clarithromycin is a safe and effective antimicrobial agent for the treatment of acute otitis media in children.

Elevated risk of anaphylactoid reaction from radiographic contrast media is associated with both beta-blocker exposure and cardiovascular disorders.

BACKGROUND: A case-control study, with both retrospective and concurrent subject selection, was performed (1) to determine whether greater risk for anaphylactoid reaction from contrast media associated with beta-blocker exposure reflects presence, or is independent of underlying cardiovascular disorder; and (2) to characterize further the risk of anaphylactoid reaction from contrast media in patients with cardiovascular disorders and patients with asthma. METHODS: Adverse reactions from intravenous contrast media were recorded in accordance with quality assurance guidelines. Anaphylactoid reactions were classified as mild to moderate (urticaria/angioedema), severe (stridor, bronchospasm, or hypotension), or major and life-threatening (hypotension with or without the need for subsequent hospitalization). Medical records from reactors were compared with those from matched (gender, age, date, and type of contrast study) controls who received conventional contrast media without adverse reaction. RESULTS: Of 34,371 intravenous contrast media procedures performed, 122 anaphylactoid reactions were recorded. The risk of anaphylactoid reaction was significantly associated with asthma (odds ratio [OR], 8.74; 95% confidence interval [CI], 2.36 to 32.35; P = .0012). The risk of bronchospasm was associated with beta-blocker exposure (OR, 3.73; 95% CI, 1.18 to 11.75; P = .025) and with asthma (OR, 16.39; 95% CI, 4.30 to 62.46; P = .0001). The risk of major and life-threatening reaction was associated with the presence of cardiovascular disorder (OR, 7.71; 95% CI, 1.04 to 57.23; P = .046). Among patients with severe reactions, the risk of hospitalization was elevated by the presence of cardiovascular disorder (P = .001), exposure to beta-blockers (OR, 7.67; 95% CI, 1.79 to 32.85; P = .029), or asthma (OR, 20.7; 95% CI, 1.21 to 355.55; P = .065). Although beta-blocker exposure and the presence of cardiovascular disorder were highly associated (chi 2 = 49, P < .001), a greater risk of bronchospasm with severe reaction was observed in nonasthmatic patients with cardiovascular disorders receiving beta-blockers (OR, 15.75; P = .023). Among reactors with asthma, receiving beta-blockers, or with a cardiovascular disorder, 60.8% (31/51) experienced severe anaphylactoid reactions, compared with 35.2% (25/71) of patients without these risk factors (OR, 3.62; P = .005). CONCLUSIONS: beta-Blocker exposure and cardiovascular disorder are both statistically significant risk factors for severe anaphylactoid reaction from contrast media. Thus, patients receiving beta-adrenergic blockers and patients with asthma, on the basis of greater risk for bronchospasm, and patients with cardiovascular disorders, on the basis of elevated risk of major and life-threatening reaction, are appropriate target populations for risk reduction measures before receiving intravenous infusion of contrast media.