373 Defining the role of CC and CXC chemokines that mediate airway inflammation from ozone-induced oxidative lung injury

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371

Abstracts

J ALLERGY CLIN IMMUNOL JANUARY 2000

The Effects of Fragrances on Respiratory Reactions of Asthmatics M McCants. SB Lehrel; R Rando, H Glindmeyer, R Gibson, L Myers. M Lopez Tulane University Medical Center, New Orleans, LA, USA Fragrances are often cited by asthmatics as initiating or exacerbating their asthma. Last year, we reported that asthmdrhinitis patients report upper (77%) and lower respiratory tract symptoms (8 I %) upon fragrance exposure. Preliminary challenge exposures with individual and mixture fragrances did not elicit a 20% or greater decline in FEVl; mean decline from baseline was 4.8%. The current study further investigated asthmatics for their responses to fragrances. Of the 77 adult asthmatics completing an allergy/asthma questionnaire, 77% (59/77) were female and 23% (I 8/77) were male; age (mean + SD) was41.3 + 10.7 years; yearsof asthma (mean + SD)22.5 + 15.0years; 77% indicated they were allergic to fragrance. Of the 38 fragrances identified as causing reactions, the top six were Red, White Diamonds, Giorgio, Charlie, Opium, and Poison. Fifteen subjects (1 I females/4 males) were selected for a standardized challenge that was developed based on previous protocols that used single or fragrance cocktail for 30 - 60 minutes/fragrance concentration at Ix - 50,000x odor threshold. For the standard challenge, subjects were sequentially exposed (5,000 x odor threshold) to fragrances (the first five listed above) randomly ordered, in an inhalation chamber for 20 minutes for each fragrance. Spirometry was performed during the last IO minutes of each exposure period. After each exposure the chamber was flushed with filtered air (4-6 exchanges). Of the I5 subjects challenged, I I (73%) had a decline of FEV, to one or more fragrances. The mean maximal decline to any fragrance exposure in FEV, from baseline was 5. I % (range 1.3 - 14.5%); no subject had a positive challenge ( 20% decline in FEV,). Red and Charlie (4 subjects/fragrance) equally elicited the most frequent decline in FEV, (Red, mean 5.6%. range 3.6 - 9.3%; Charlie, mean 3.5%. range I .3 - 6.5%) followed by (I subject /fragrance), Giorgio (14.5%). Opium (3.4%). and White Diamonds (2.2%). One subject had an equal decline (3.6%) to both Red and Charlie. During the last IO minutes of exposure, subjective symptoms were scored to each fragrance; a two-step or greater increase from baseline was considered significant (positive). The total number of positive symptom increases to fragrance were: I8 (Red), I6 (Georgia,), I3 (Opium), 1 I (Charlie), and 8 (White Diamonds). The number of subjects reporting positive responses were: 87% (nasal), 80% (odor/throat each). 73% (overall acceptability), 67%(chest), and 53 % (annoyance). These studies support our earlier report that fragrances cause frequently respiratory symptoms in asthmatic individuals. However, the degree of decline in FEVI was much less than that expected from subjects’ clinical histories. It may be that the symptoms reported by asthmatics were due in part to the effect on upper airways of which 83% of the asthmatics complained in this study. Different fragrances differ with regard to the number and intensity of reactions that occur.

372 Is There Any Relationship tization to House dren in Santiago hing*,

C Diazf,

Between Air Pollution and IgE SensiDust Mite and Lolium Perenne in School Chilof Chile? SE Soto LavIn*, G L&n*, E Schei-

E Wut,

AM

Von ChrismaP,

M Mansilla$,

J Inos-

R SorensenI *Austral University of Chile tuniversity of Chile .$UFRO PLSUMC Nasal epithelium is the first barrier between allergens and ambient air pollution. Our preliminary report showed that children not exposed to pollutants had a good production of IL-8 by nasal epitheIial cells and protein levels in nasal lavage were greater than children exposed chronically. It is not known if there is an association between chronically exposition to air pollutans and the sensitization to differents allergens. Our rroza#,

study was done in random samples of school children aged 6 and 7 years old. 46 living in Santiago of Chile, chronically exposed to 03 and suspended particles, I9 children living in San Felipe without air pollution and 70 living inTemuco City with high amounts of suspended particles. A written consent was asked to their parents in all cases. A blood sample was obtained. Unicap system was used to measure specific IgE to House Dust Mite and Lolium Perenne (range 0.35 to 100 KUA/L). Statistical analysis was done using the one way Analysis of Variance considering the geographical location as a factor. The p-value obtained was 0.61071 for House Dust Mite and 0.84050 for Lolium Perenne. Therefore. we conclude that the children living in Stgo, San Felipe and Temuco City have the same risk to be sensitized to House Dust Mite and Lolium Perenne. 373

Defining The Role Of CC And CXC Chemokines That Mediate Airway Inflammation From Ozone-Induced Oxidative Lung Injury Lidia Michalec. BK Choudhury, Michael Left-Brown. Edward M Posrlethwair. S Sur NIH Asthma Center and the Department of Internal Medicine, University of Texas Medical Branch. Galveston. TX Ozone (03) exposure causes oxidative lung injury that induces an influx of inflammatory cells into the airways associated with chemokine production. The present study was designed to identify and elucidate the role of CC and CXC chemokines in 03 induced airway inflammation. In the experimental groups. female Balb/c mice were exposed to 0.2 ppm or 0.8 ppm 03 for 6 hours in an ozone exposure chamber. In the control group, mice were exposed to air in another exposure chamber. The experimental and control animals were sacrificed and a BAL was performed 6 hours, 24 hours. 48 hours and 144 hours after initiation of ozone or air exposure. Exposure to air or low dose 03 (0.2 ppm) did not alter the cells in BAL at any time. In contrast, 03 (0.8 ppm) increased the number of neutrophils predominantly at 24 hours [0.019 + 0.01 (air control group) vs 14.25 22.95 (03 group) x 104/ml: pf; 0.05). 03 (0.8 ppm) increased macrophages numbers starting at 6 hours, and peaking at 48 hours [I .24+0.37: (air). vs 17.75k2.18 x 104/ml, (03): pf 0.05]. Whole lung CC and CXC chemokine (KC, MIP-2, MIP-la, IP-10. MIG. MCP-3, Eotaxin, RANTES) mRNA expression was quantified by the ratio of the intensity of the chemokine band relative to b2M (a housekeeping gene) following RT-PCR: INCREASE IN RT-PCR INCREASE IN RT-PCR BAND INTENSITY, BAND INTENSITY, 6 HOURS AFTER 24 HOURS AFTER 0.8 PPM CC OR CXC 0.8 PPM CHEMOKINE 03 VS AIR 03 VS AIR KC

10.5

NO DIFFERENCE

MIP-2

13.8

NO DIFFERENCE

EOTAXIN

9.1

NO DIFFERENCE

MIP-1A

3.8

2.1

MIG

4.4

3.2

MCP-3

13.1

4.5

IP-10

10.6

3.3

RANTES

NO DIFFERENCE

NO DIFFERENCE

To evaluate the role of the six chemokines upregulated by 03 in mediating airway inflammation induced by 03, seven groups of mice were treated intranasally with normal rabbit IgG (control IgG group) or polyclonal rabbit anti-mouse IgG against one of six murine

Abstracts

J ALLERGY CLIN IMMUNOL VOLUME

chemokines: KC, MIP-2, MCP-3, MIP-la. IP-IO, and eotaxin. One hour after antibody administration, the mice were exposed to 0.8 ppm ozone for 6 hours. As expected, the control IgG group demonstrated a vigorous inflammatory response to 03 exposure. Compared to the control IgG group, all six antibodies decreased the total number of cells by 50 to 72%; pf; 0.01. Likewise, all six antibodies strongly inhibited neutrophilic inflammation by 67 to 85 %; p f; 0.01. However, macrophagic inflammation was attenuated only by antibodies to KC (52%; pf; 0.05) and IP-10 (44%; pf; 0.01). This is the first report demonstrating that 03 - induced neutrophilic lung inflammation is mediated by the chemokines KC, MIP-2, MCP-3, MIP- la, IP- IO, and eotaxin. whereas, macrophagic inflammation is mediated by KC and IP-IO. 374

375

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105, NUMBER 1, PART 2

Risk Factors for Asthma in a Cohort of Adolescents R McConnell*, K Berhane*, R Gilliland*, T Islam*. E Avol*, S London f. J Gauderrnan*. H Margolis. H Margolis$. J Peters* *University of Southem California tNational Institute of Environmental Health Science SCalifomia Air Resources Board Risk factors for asthma were evaluated in a cohort of school children. Children and their parents were recruited in from schools in neighborhoods with stable, largely middle-income populations in 12 communities in Southern California. One hundred fifty fourth graders (aged 9-10 years), 75 seventh graders (12-13 years) and 75 tenth graders (15-16 years) from each community completed a baseline questionnaire with help from their parents in 1993, and an additional 300 fourth graders from each community completed a baseline questionnaire in 1996. Three thousand five hundred thirty-five children without a history of asthma were available for follow-up studies; 2752 (78%) of these had no history of wheezing, and 783 (22%) reported wheezing on the initial questionnaire. Reports of new diagnoses of asthma were assessed by yearly questionnaire administered during up to 5 years of follow-up. Of 265 children who subsequently developed asthma, a total of 163 reported no wheeze at baseline and 102 had reported a wheezy illness. The original questionnaires of these children have been examined and compared with those completed by children who did not develop asthma. In children with a history of wheeze, hamsters and birds as pets were associated with a significantly increased risk of developing asthma. In children with no history of wheezing, a humidifier in the home, any pet, or a dog were all associated with a modestly increased risk of developing asthma. Swimming was associated with a reduced risk. The risk of developing asthma was increased in those who participated in team sports and the risk increased with the number of sports played. Among the entire cohort, additional risk factors included the reported time spent outside. Possible explanations of these findings include the higher dose of air pollutants in those active out of doors; or the likelihood that physical activity might lead to the detection of bronchospasm and hence to a diagnosis of asthma. The Effect of Exposure to Environmental Tobacco Smoke on Clinical Findings in Asthmatic Schoolchildren G Giiler; ii &es. A Kilig, Z Tamay University of Istanbul, Faculty of Medicine, Department of Pediatric Allergy and Pulmonology, Istanbul, Turkey The aim of this study was to investigate the effects of exposure to environmental tobacco smoke (ETS) during the children’s lifetime, beginning from intrauterine period on severity score and pulmonary functions in asthmatic schoolchildren who are on prophylactic therapy. Forty-seven patients (lSF, 32M), aged between 5-15 years (median: I I years) were included to the study. Patients with FEV, reversibility > 75% were accepted as asthmatics. Patients with other illnesses such as tuberculosis, congenital heart disease, immune deficiency, cystic fibrosis and gastroesophageal reflux were excluded from the study. A detailed questionnaire was used to determine the amount and time of exposure to ETS. Urinary cotinine/creatinine

ratio was used as a parameter of current exposure. The patients were followed up to I year and pulmonary functions were evaluated regularly. Parameters determining asthma severity scores and pulmonary functions of the patients did not show any correlation with cotinine/ creatinine ratios. There were positive relationships with the number of cigarettes smoked by the mothers currently (p:O.o08) and during pregnancy (p:O.O06). The number of cigarettes smoked by the fathers (p:O.O4) and the amount of passive smoking of mothers during pregnancy (p:O.O4) also showed positive correlations with asthma sevetity. FEF25-75 reversibility was significantly higher in children of smoking mothers both currently (p:O.O3) and during pregnancy (p:O.OOl). PEF reversibility was also significantly higher in children of the mothers who smoked during pregnancy. We have established that ETS, primarily smoked by the mother during various periods of life have long term effects on clinical features of asthma in schoolchildren. Pulmonary reversibility tests are also affected not only by current smoking habits of the mother, but also by active and passive smoking of the mother during pregnancy. These effects are found to be prominent despite the optimal asthma therapy.

376 Pigeon

Fancier’s Lung (PFL) by an Occasional Exposure to Pigeons M Rosal, MJ Torres, JL Rodriguez, S Posadas. J Pkrez, E Perez, C Mayorga, L Leyva. MJ Blanca Research Unit of Allergic Diseases, Carlos Haya Hospital, Mfilaga, ESPARA Although PFL (a form of hypersensitivity pneumonitis) is an occupational disease, there are cases of appearance of the same occurring after non occupational or minima1 exposure. This may creates confusion with other diseases. We studied a case of a child who presented a typical clinical feature and a X-ray image suggestive with tuberculosis, and after a careful evaluation it was proved to have PFL. A three years old child developed an episode of cough, malaise, dyspnea and loss of weight I5 days before being evaluated. The exploration showed cyanosis, desnutrition and taquipnea, and a pulmonary X-ray examen showed a bilateral micronodular infiltrate with hiliar adenopathies, confirmed afterly by TAC. No antecedent or suspect of pulmonary tuberculosis in the family environment was found. Occasional exposure to pigeons in the days previous to the disease was reported. The blood cell count gave the following values: lymphocytes CD3+ (59%). CD4+ (27%). CD8+ (26%). CDl9+ (31%). CDI6+ (10%). CD4+/CD8+ (I, I). The lymphocyte count in bronchoalveolar lavage showed a similar pattern. After reexposure the child developed the same symptoms as reported above and the treatment with corticoids was initiated with improvement in a period lower than 24 hours. Specific IgG antibodies to pigeon serum proteins were determined in patient serum and exposed controls. Additionally, the specificity of IgG recognition was tested by ELISA inhibition. The capacity of lymphocytes to proliferate in the presence of pigeon antigens was tested by a lymphocyte transformation test (LIT). Very high values of specific IgG antibodies were found in patient serum. These were also present in controls but negative in an exposed subject. A study of the proliferative response of lymphocytes showed a persistent response in the affected subject and in non exposed controls. These data confirm that PFL may occur in subjects with a minimal exposure and may simulate other disease. The undertaking of the opportune studies after a careful evaluation led to the correct diagnosis. In addition, the LITresults along with those ELISA ones, showed that PFL can be not only a disease characteristic of professional pigeon breeders exposed to a repeated inhalation of organic dusts, but also a disease of subjects who have suffered a minimum contact with these animals, as consequence of an extremely high sensitivity.