Profile of the asthmatic child in Lebanon.
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Biomedical subjects
Publications and source records attributed to A Hejjaoui.
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Specific immunotherapy (SIT) using a standardized mite extract is effective and safe when administered under optimal conditions. However, the duration of its effectiveness after cessation of treatment remains unknown. Forty asthmatic subjects who had received SIT with a standardized Dermatophagoides pteronyssinus (Der p) extract under the same protocol were studied. All had received SIT for a period of 12-96 months and were not receiving pharmacologic treatment. The FEV1 was within normal range in all patients. After cessation of treatment, patients were followed for up to 3 years at 6-month intervals. The patient was considered to have relapsed when symptoms of asthma and/or rhinitis occurred and/or when pulmonary function tests were impaired. Skin tests with increasing concentrations of Der p were carried out before and at the end of SIT. Forty-five percent of the patients did not relapse. The duration of efficacy of SIT was related to the duration of SIT itself (P < 0.04). Most patients who did not relapse had a decrease in skin test reactivity at the end of SIT, whereas most patients who relapsed did not show any change (P < 0.003). The duration of efficacy of SIT after its cessation depends upon the duration of SIT and may be predicted by the effect of SIT on skin tests.
The heterogeneity of pollen-allergic persons is well known but poorly characterized. Cypress is one of the major pollen-producing plants of the Mediterranean area. A study was undertaken to characterize the symptoms presented by patients allergic to cypress pollen and the heterogeneity of the IgE immune response between patients allergic only to cypress pollen and those who are polysensitized. Eighty-nine patients allergic to cypress pollen were studied, 26 being allergic only to cypress pollen. The IgE response was assessed by skin prick tests and the titration of serum total IgE and cypress-specific IgE by RAST. Clinical reactivity was assessed by symptom scores during the cypress pollen season and skin tests. Pollen counts were obtained. The clinical reactivity was similar in both patient groups. Rhinitis was present in all patients, conjunctivitis in 73.7-88.5%, and asthma in only 7.4-19.2%. The age of onset of symptoms caused by cypress pollen allergy was significantly greater in patients allergic to cypress pollen only. Total serum IgE was within the normal range in the cypress pollen group and significantly lower than in the polysensitized groups. Cypress pollen RAST was higher in the polysensitized group. We concluded that conjunctivitis is particularly common in cypress pollen allergy. Patients allergic only to cypress pollen may be unique in their way of expressing serum total IgE levels.
Specific immunotherapy with standardized extracts administered by a rush protocol can induce systemic reactions (SRs). A prospective study was conducted in 454 pollen-allergic patients (aged 5 to 62 years) (1) to compare the incidence of SRs during a 3-day rush or step protocol, (2) to determine if patients presenting pollen asthma or those allergic to multiple pollen species would have an increased incidence of SRs, and (3) to attempt to decrease SRs. According to their sensitivity, patients received standardized extracts of orchard grass, and/or Parietaria, and/or olive, and/or plane-tree pollen with the same allergenically bioequivalent maintenance dose. Patients 10 years of age and older received 2000 BU; patients younger than 10 years, 1000 BU. The occurrence of SRs was carefully monitored. The incidence of SRs per patient ranged from 2.6% to 31.1%. With the rush protocol, there was a significant decrease in SRs after premedication (p less than 0.015). Severe SRs decreased further when the increase in doses was stopped because large local reactions occurred. Step protocol was only slightly better tolerated than rush protocol. Bronchial adverse reactions occurred more often in patients presenting asthma during previous pollen seasons. No reaction started 45 minutes or later after the last injection.
The IgE response of patients only allergic to grass pollens differs from response of patients allergic to multiple-pollen species. The IgE immunoblots to orchard-grass pollens confirmed that polysensitized patients had more proteins revealed than patients only allergic to grass pollens. To determine if both groups of patients present a different response toward specific immunotherapy (IT), a double-blind, placebo-controlled study was performed in 70 patients. Patients receiving the active treatment had a rush IT with either a standardized orchard grass-pollen extract or with a standardized mixed-pollen extract prepared, depending on the sensitivity of the patients. The maintenance dose was defined as that dose effective in grass-pollen IT in previous experiments. The same equipotent maintenance dose was administered for all pollen species. Symptom-medication scores during the pollen season and nasal challenge with orchard grass-pollen grains demonstrated that grass pollen-allergic patients had a significantly improved efficacy by comparison to placebo treatment, whereas polysensitized patients had a nonsignificant improvement. Serum grass-pollen IgG was significantly increased after IT in both treated groups. This study demonstrate that the response toward specific IT differs in patients only allergic to grass pollens by comparison to polysensitized patients.
The heterogeneity of pollen-allergic individuals is well-known but poorly characterized. Twenty-six patients were studied to characterize their immunologic and clinical patterns. Thirteen patients were allergic only to grass pollens, and 13 other patients were allergic to grass-pollen and other pollen species, including Cupressaceae, plane tree, olive, and Parietaria. The IgE response was assessed by the titration of serum total IgE and orchard grass-specific IgE, as well as by IgE immunoblots to orchard-grass pollens. Clinical reactivity was assessed by nasal challenge with orchard-grass pollens before the pollen season and nasal and bronchial symptom-medication scores between April 1 and June 15. Pollen counts were obtained during this period of survey. Polysensitized patients had significantly increased levels of serum total and specific IgE and a greater heterogeneity of IgE immunoblots, suggesting an enhanced qualitative and quantitative IgE immune response. Polysensitized patients had nasal and bronchial symptoms occurring earlier than grass pollen-allergic individuals, confirming the priming effect caused by other plans flowering with an earlier season for both nasal and bronchial mucosa. Alternatively, the early symptoms may be attributable to the tree pollens or might reflect the higher grass-pollen IgE level in the polysensitized group. Bronchial symptoms appeared a few weeks after nasal symptoms. Nasal challenges were similar in both groups, and the severity of nasal symptoms during the season was not significantly different in both groups, suggesting that the intensity of symptoms is not related to the sensitization nor to the IgE immune response of the subjects.
Mast cells and histamine-mediated reactions may be altered in patients with cancer. In an attempt to characterize the possible skin defects in patients with cancer, we tested 22 patients suffering from lung cancers, 30 from breast cancers, and 30 age-matched normal individuals, using several compounds, in investigating the pathophysiology of the skin response. Histamine hydrochloride (10 and 100 mg/ml) and codeine phosphate (9%) were tested by prick test. Substance P (50 and 500 ng per injection site), phentolamine (20 micrograms per injection site), and carbachol (1 microgram per injection site) were tested by intradermal skin tests. Skin mast cells were also microscopically examined in 10 patients with lung cancer, five with breast cancer, and 10 normal subjects. The mean wheal sizes induced by all the tested substances were similar in patients with cancer and chronic bronchitis and in normal individuals. The flare to histamine, codeine phosphate, and substance P was completely abolished in 7/22 patients with lung cancer, but the lack of flare was not related to the age of the patients, nor to the staging of cancer, nor to metastasis. The mean numbers of alcian blue-stained or toluidine blue-stained positive mast cells were similar in normal subjects and in subjects with cancer. This study does not confirm the skin hyporeactivity of patients with cancer.
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Specific immunotherapy is ineffective with unstandardized mold extracts. A double-blind, placebo-controlled study was performed in 24 patients (5 to 56 years of age) only allergic to Alternaria. The extract was standardized by isoelectric focusing, crossed immunoelectrophoresis, crossed radioimmunoelectrophoresis, RAST inhibition, and skin tests and contained allergen Alternaria major allergen a I and antigen B. Thirteen patients received the active treatment, and 11 received the placebo. Immunotherapy was started by a 2-day rush protocol; maintenance injections were administered for 1 year. The patient's self-evaluation of the treatment was significantly (p less than 0.001) lower in the placebo-treated group. Global symptom-medication scores, including asthma and rhinoconjunctivitis, were significantly (p less than 0.005) lower in the actively treated group. Nasal challenges with Alternaria extract were performed before immunotherapy and after 1 year of treatment. There was no difference in the placebo-treated group and a significantly (p less than 0.01) increased mean provocative dose in the actively treated group. Skin tests were significantly reduced in the actively treated group. Specific IgG increased significantly in the actively treated group and were stable in the placebo-treated group. There was a significant correlation between nasal challenges and nasal symptom-medication scores (p less than 0.03) or the patient's self-evaluation of efficacy (p less than 0.05). This study demonstrated that patients only sensitized to Alternaria benefit from specific immunotherapy with a standardized Alternaria extract.
Specific immunotherapy with standardized extracts can induce systemic reactions (SRs), possibly increased by a rush immunotherapy (RIT) protocol. A prospective study in 1152 mite-allergic patients (3 to 63 years of age) examined the incidence of SRs during an RIT or a step protocol. All patients received the same standardized extract of Dermatophagoides pteronyssinus with the same maintenance dose. In the first group, 290 patients had an RIT protocol without any preventive measure. In a second group, the prevention of SRs during RIT was attempted by pretreating 160 patients with methylprednisolone (0.5 mg/kg/day), ketotifen (2 mg/day), and theophylline (10 mg/kg/day). In a third group (479 patients), the same pretreatment was associated with preventive measures and with FEV1 results and the occurrence of large local reactions. A fourth group consisted of 223 patients who received a step protocol with the same pretreatment and preventive measures. The incidence of SRs per patient was 36.2% with RIT alone, 16.2% when the pretreatment was added, and 7.2% when pretreatment and preventive measures were used. Patients receiving the step protocol had 5.4% SRs. Adrenaline had to be used from 10.0%, 4.6%, 0.2%, and 0.2%, respectively. No reaction started 45 minutes or later after the last injection. Children younger than 5 years of age had a significantly greater number of SR.
Specific immunotherapy is still widely used in grass-pollen allergy, but its side effects may limit its use. We tested the safety and efficacy of a formalinized high-molecular-weight allergoid prepared from a mixed grass-pollen extract with two injection schedules in a double-blind, placebo-controlled study. Eighteen patients received placebo, 19 received the low-dose schedule (maximal dose: 2000 PNU) and 20 received the high-dose schedule (maximal dose: 10,000 PNU). Only one patient presented a systemic reaction of moderate severity for a dose of 1200 PNU. Before the onset of the pollen season, patients had a nasal challenge with orchard grass-pollen grains, a skin test titration, and the titration of serum-specific IgG. Both groups of patients presented a significant reduction in nasal and skin sensitivities and a significant increase in IgG compared to placebo. Symptoms and medications for rhinitis and asthma were studied during the season, and both groups receiving allergoids had a significant reduction of symptom-medication scores for nasal and bronchial symptoms. There was a highly significant correlation between nasal symptom-medication scores during the season and the results of nasal challenges. High-molecular-weight allergoids are safe and effective.
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Specific immunotherapy can induce severe systemic reactions (SRs), especially in patients with asthma. It also appears that potent standardized extracts may be more often involved in the generation of SRs than other extracts. Since these SRs may be potentially life threatening, it is desirable to predict their onset. A prospective study was carried out in 125 mite-allergic subjects with asthma ranging in age from 4 to 57 years to assess the incidence of SRs during a rush immunotherapy (RIT) protocol and maintenance injections and to attempt to predict the onset of the SRs. All patients received the same standardized extract of Dermatophagoides pteronyssinus with the same RIT and the same maintenance dose (3000 BU in subjects older than 10 years and 1500 BU in children younger than 10 years). Patients were carefully monitored during the RIT protocol, and possible SRs were followed for up to 2 hours after injections. Patients then received maintenance injections for a mean duration of 18.2 +/- 5.6 months. During maintenance injections, patients were under supervision of a physician for 30 minutes. Within 2 weeks before the RIT, all patients older than 6 years had a pulmonary function test, skin prick test end point with the standardized D. pteronyssinus extract, and RAST. The severity of asthma was examined with the score of Aas. Forty-seven patients had an SR during the RIT protocol: four mild generalized urticaria, 35 asthma exacerbations, and eight anaphylactic shocks. None of the patients had to be admitted to an intensive care unit. Most SRs started within 15 minutes, and none of the SRs started 45 minutes or later after the last injection.(ABSTRACT TRUNCATED AT 250 WORDS)
Specific immunotherapy with unmodified formalinized allergoids is effective in grass-pollen allergy, but systemic reactions have been observed. A high-molecular-weight formalinized allergoid (HMW-GOID) was fractionated by gel filtration, retaining molecules of greater than 85,000 daltons in the expectation of improving safety without sacrificing efficacy. HMW-GOID and unfractionated allergoid (GOID) had a similar allergenic activity assessed by RAST inhibition, but the HMW-GOID preparation was 65 times less reactive when it was tested by skin prick test than the GOID preparation. A double-blind, placebo-controlled study was carried out in grass pollen-allergic patients with placebo (14 patients), GOID (15 patients), and HMW-GOID (13 patients). An additional group of 18 patients was treated by a rush schedule with a standardized orchard grass-pollen extract. A similar mean cumulative dose was administered with both allergoids. The fractionated allergoid only elicited minor systemic reactions similar to reactions elicited by placebo, whereas 20% of patients treated by GOID and 5.5% of patients receiving the standardized extract had a severe systemic reaction. For rhinitis, conjunctivitis, and asthma, the HMW-GOID and the standardized extract had a similar efficacy, significantly greater than placebo. GOID was less effective than the other two active treatments but was significantly more effective than placebo treatment for asthma and conjunctivitis.
Specific immunotherapy is effective in alleviating symptoms in grass pollen-induced rhinitis, but there are no clear data demonstrating a correlation between symptom-medication scores and objective parameters. Twenty-five patients taking part in a double-blind, placebo-controlled immunotherapy with mixed grass pollen-formalinized allergoids were studied. All patients had the same investigations. Symptom-medication scores were significantly (p less than 0.005, Mann-Whitney U test) reduced in the treated group by comparison to the placebo-treated patients. Nasal challenges performed with threefold increasing numbers of orchard grass-pollen grains demonstrated that patients treated with allergoid tolerated a significantly (p less than 0.005, Wilcoxon W test) greater number of grains after treatment, whereas there was no mean difference in the placebo-treated patients. There was a significant (p less than 0.005, Spearman rank-correlation) correlation between nasal challenges and symptom scores during the season. The skin prick test end point was significantly (p less than 0.001, Wilcoxon W test) reduced after treatment in the allergoid-treated group and remained unchanged in the placebo-treated group. There was a significant (p less than 0.001) correlation between the skin prick test end point and symptom scores during the season. Serum grass-pollen IgG titrated by a solid-phase radioimmunoassay with Staphylococcus A protein was significantly (p less than 0.01, Wilcoxon W test) increased after treatment with allergoid, but there was no significant correlation between IgG titer and symptom scores during the season. Serum grass-pollen IgE increased (p less than 0.04, Wilcoxon W test) in the treated group but there was no correlation with symptom scores.
House dust mites of the species Dermatophagoides pteronyssinus (Dpt) represent one of the major allergens inducing asthma. However, a strict allergy to Dpt is not always observed in Dpt-allergic patients, since nonallergic and other allergic triggering factors often coexist. It was suggested that specific immunotherapy with house dust-mite extracts is more effective in children than in adults. A controlled study was undertaken in 215 Dpt-allergic patients with asthma ranging in age from 3 to 72 years (mean +/- SD, 28.2 +/- 10.9 years) to investigate parameters that might predict the efficacy of specific immunotherapy before it is started; 171 patients received a rush immunotherapy protocol with a standardized Dpt extract and, subsequently, maintenance injections with 3000 BU of this extract, and 44 patients served as a control group. Before immunotherapy, all patients had a complete evaluation of the severity of asthma by symptom-medication scores and a pulmonary function test, as well as a study of other triggering factors by checking on seasonal and perennial allergens, sinusitis, and other possible causes, such as aspirin intolerance; 196 patients were investigated between 9 and 12 months after the onset of the survey by means of pulmonary function tests and symptom-medication scores. Medications were adapted according to peak flow rates. It was observed that patients with chronic sinusitis, and/or aspirin intolerance, and/or other perennial allergies did not benefit from specific immunotherapy; therefore, the treatment of a major etiologic factor did not demonstrate improvement in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Busereline acetate is an LH-RH agonist that was found to induce local reactions at the injection site or generalized minor skin reactions in some patients. Since these reactions may represent the first reaction of systemic anaphylaxis, we tested the non-specific histamine releasing activity of this drug by intradermal skin tests. It was found that all subjects tested had a positive wheal and flare reaction, the flare being significantly decreased by terfenadine. Benzyl alcohol, the preservative used in commercial preparation of busereline acetate, did not elicit a positive wheal and flare reaction in two patients who had experienced a clinically noticeable reaction. It is concluded that busereline is likely to be a non-specific histamine releasing compound.