Allergic bronchopulmonary aspergillosis as presenting sign of cystic fibrosis in an elderly man.

BACKGROUND: Although cystic fibrosis is the most common genetic disorder of children, its heterogeneous spectrum of severity lends itself to underdiagnosis in the older adult patient population where the index of suspicion is not high. METHODS: We report a 60-year-old Hispanic man with asthma who presented with progressive dyspnea and wheezing unresponsive to inhaled corticosteroid treatment. Additionally, he had clinical findings and a past history suggestive of cystic fibrosis. Skin testing, radiography and laboratory studies were completed to evaluate for allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis. RESULTS: Test results revealed peripheral eosinophilia and hyper IgE. Skin testing to Aspergillus fumigatus (Af) was positive. IgG, IgM, and Af specific antibodies were present. High resolution CT scan showed central bronchiectasis. Sweat tests were positive on two separate occasions and gene analysis showed our patient to have a positive gene mutation at D127ON/D127ON. CONCLUSION: Cystic fibrosis should be suspected in the older adult patient with a compatible clinical presentation.

Bone mineral density in women with asthma on long-term inhaled corticosteroid therapy.

BACKGROUND: Inhaled corticosteroids (ICS) have become first line agents in the management of moderate-to-severe asthma. Long-term use of ICS is associated with decreased bone mineral density (BMD). OBJECTIVE: To investigate the prevalence of BMD loss and its severity in women with asthma on long-term ICS. METHODS: Fifty-six women with asthma on long-term ICS, attending an inner-city allergy clinic were selected to undergo bone densitometry in order to evaluate the association between BMD and the long-term use of ICS at different dose ranges. RESULTS: Women (60.7%) had decreased BMD either at the lumbar spine or hip region. Among postmenopausal women, 17.1% of those <65 years and 42.9% of those > or =65 years had osteoporosis compared with 5.7% (95% CI-3.9% to 8.5%) of those <65 and 29.3% (95% CI-25.7%-33.5%) of those > or =65 years reported in the NHANES III survey. The prevalence of low BMD increased as ICS dose increased from 5% in the low dose group to 50% in the high dose group (P < .002). There were significant linear trends of decline by dose in mean BMD for the hip (P < .001) and the lumbar spine (P < .002). Women who received medium or high doses of ICS had significantly greater bone loss than those receiving low doses. CONCLUSION: The findings of increasing BMD loss with increasing ICS dose reinforce the necessity to monitor BMD periodically in women on ICS, particularly in the high risk postmenopausal group and those on medium to high doses. There should be a concurrent continual attempt to lower the dose by supplemental nonsteroidal controller medications and providing nutritional and pharmacologic treatment of identified BMD loss in these patients.

Superior clinical outcomes of inner city asthma patients treated in an allergy clinic.

BACKGROUND: Asthma morbidity and mortality continue to increase especially in the inner cities despite medical advances in disease management. OBJECTIVE: To investigate the clinical outcomes of inner city asthma patients treated in an allergy clinic. METHODS: Phase 1 involved random review of medical records of 100 asthma patients treated in an allergy clinic for 2 consecutive years, assessing the frequency of hospitalizations, emergency room visits (ERV) and asthma severity during three periods; 1 year prior to initial visit (year 0) and during the first (year 1) and second (year 2) years of intervention. Phase 2 involved administration of quality of life (QOL) survey to 23 patients volunteered from allergy clinic (group I), and 21 patients volunteered from emergency room (group II), treated by primary care or emergency room physicians during the previous year. RESULTS: The frequency of hospitalizations and ERV significantly declined over time (P < .001) with greatest declines during year 1. Disease severity of all patients significantly declined over time (P < .001); good compliers had significant improvement over poor compliers (P < .023). Quality of life scores were significantly lower for both groups than for the general population; and although the scores were higher in the allergy clinic group than in the non-allergy clinic group, significant differences were achieved only in mental health and social functioning domains. CONCLUSIONS: Patients treated in an allergy clinic demonstrate superior clinical outcomes.

Training perception of air flow obstruction in asthmatics.

Eighteen asthmatics, aged 7 to 43, rated their breathing on a scale of 0 to 5 (worst to best). They were then informed of their predicted normal peak expiratory flow rate (PEFR) and instructed in proper PEFR measurement. Each subject then estimated and measured PEFR under physician supervision and subsequently rated breathing, estimated and measured PEFR at home twice daily recording the observations. At the initial home observation, the correlation coefficient (r1) between estimated and measured PEFR was .98. After ten observations r1 was greater than or equal to .97 in all 18 subjects (group mean .99). The r1 remained unchanged in those subjects who completed 28 and 42 observations. The r1 was .98 when only the observations where measured PEFR was less than 20% predicted were considered, demonstrating the validity of the relationship during abnormal expiratory flow. Multiple regression analysis showed no significant trend in the difference between estimated and measured PEFR over time after the initial observation. Of 12 subjects, 4 were significant underestimators of PEFR and 3 were overestimators, but the magnitude of either tendency was relatively small. The correlation coefficient (r2) between a subjective verbal breathing score and measured PEFR ranged from -.23 to .92 on an individual basis over the three time periods, with statistically significant group mean values of .37, .39, and .45 at 10, 28, and 42 observations, respectively. The r2 for observations where measured PEFR was abnormal was only .14 and not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric protection by misoprostol against 1,300 mg of aspirin. An endoscopic dose-response study.

Misoprostol at a dose of 200 micrograms inhibits gastric acid secretion and protects the gastric mucosa against the injurious effects of a single 1,300-mg dose of aspirin. The purpose of this study was to determine whether lower subantisecretory doses of misoprostol protect the gastric mucosa in this single-dose aspirin model. Protection was defined as no more than 10 hemorrhagic spots and no more than two hemorrhagic streaks. A total of 140 men participated in the two phases of the study. In the first phase, groups of 10 subjects each received placebo or misoprostol in doses of 200 micrograms, 100 micrograms, 50 micrograms, or 25 micrograms in a double-blind design. All misoprostol doses protected 50 to 70 percent of subjects as compared with 20 percent of subjects in the placebo group. To expand the number of observations, 90 additional subjects in groups of 30 each were evaluated after receiving misoprostol 50 micrograms or 25 micrograms or placebo. Misoprostol 50 micrograms protected 14 of 30 subjects (47 percent), 25 micrograms protected 11 of 30 (37 percent), and placebo protected six of 30 (20 percent). The dose-response trend was statistically significant (p less than 0.05). It is concluded that misoprostol protects the gastric mucosa against a single 1,300-mg dose of aspirin and that there is a significant dose-response relationship.

Serum lactate dehydrogenase levels in adults and children with acquired immune deficiency syndrome (AIDS) and AIDS-related complex: possible indicator of B cell lymphoproliferation and disease activity. Effect of intravenous gammaglobulin on enzyme levels.

Twenty-seven of 33 patients with the acquired immune deficiency syndrome (AIDS) or AIDS-related complex (16 adults and 17 children) demonstrated significant elevation of serum lactate dehydrogenase activity, occurring in the isomorphic distribution. Serum lactate dehydrogenase activity was the highest in all nine patients with acute Pneumocystis carinii pneumonitis, in seven of whom extensive interstitial pulmonary infiltrates with lymphocytes and plasma cells were documented. Lactate dehydrogenase activity was also significantly elevated on a long-term basis in all 17 pediatric patients with non-Pneumocystis lymphoid interstitial pneumonitis. Clinical resolution of Pneumocystis carinii pneumonitis was associated with a decline in lactate dehydrogenase activity. Periodic intravenous gammaglobulin was more effective than conventional therapy (trimethoprim/sulfamethoxazole and pentamidine) in achieving clinical and immunologic improvement and reduction of serum lactate dehydrogenase activity in patients with Pneumocystis carinii pneumonitis. Intravenous gammaglobulin was also more effective in patients with AIDS and non-Pneumocystis carinii pneumonitis and lymphoid interstitial pneumonitis. Lactate dehydrogenase activity declined to normal, at least temporarily, in nine of 12 intravenous gammaglobulin-treated patients as compared with only two of 12 untreated patients. Six adult patients with AIDS or AIDS-related complex and no interstitial pneumonitis exhibited normal lactate dehydrogenase levels. These findings suggest that serum lactate dehydrogenase activity in patients with AIDS or AIDS-related complex may be a useful indicator of pulmonary interstitial inflammation. As such, it may be utilized to predict disease course and monitor response to intravenous gammaglobulin treatment.

Isolation of membrane attack complex of complement from myelin membranes treated with serum complement.

The interaction between complement and myelin membranes and its possible role in myelin damage and in the disposal of damaged myelin in vivo is of interest because activation of complement generates both opsonin(s) and membrane attack complex of complement. In our studies on the role of complement in demyelination, we have shown that isolated myelin activates serum complement in the absence of myelin-specific antibody and that membrane attack complex of complement is the required factor in antibody-mediated demyelination of mouse cerebellar explant cultures. In the present study, we examined whether activation of serum complement by myelin is associated with the formation of membrane attack complex of complement in myelin membranes. Extracts of myelin-associated proteins following incubation of myelin with fresh serum were studied by ultracentrifugation on a sucrose density gradient for detection of C5b-9 neoantigen. The subunit structure of C5b-9 was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, electroblotting, and immunostaining. Results indicate that the macromolecular complex consisting of late-acting complement components, C5-C9, was assembled in the target myelin membranes.

Effect of erythrocyte membrane modulation by lysolecithin on complement-mediated lysis.

Alterations of the physiochemical properties of membranes, such as acyl chain length of phospholipids, cholesterol content, and disturbance of the bilayer packing, affect the efficiency of membrane attack by C5b-9. In the present study, we explored the effect of lysolecithin (LL), a naturally occurring derivative of membrane phospholipids, on membrane damage by C5b-9. Sublytic doses of the L isomer of palmitoyl-lysolecithin were incorporated into the erythrocyte membranes of guinea pig (gpE) or sheep (shE) and the cells were then lysed with C5b6-C9. Marked enhancement of complement-mediated lysis was observed with LL-treated gpE after 2 hr of incubation, whereas the lytic enhancement was either nil or only marginal in shE. Studies on the kinetics of LL incorporation and metabolism in gpE membranes with 14C-LL showed that LL was rapidly incorporated and catabolized to generate free fatty acid (FA). Maximal accumulation of labeled FA in the membrane and loss of membrane-incorporated LL, resulting in approximately equimolar amounts of LL and FA, occurred at 2 hr, concomitant with enhancement of complement-mediated lysis. In shE such a breakdown of LL occurred only minimally. This quantitative difference in LL breakdown between gpE and shE was in accord with lysophospholipase activity that was two and one-half to seven times more active in gpE than shE membranes. When an ether-linked analog of LL (1-O-hexadecyl-sn-phosphorylcholine), which is resistant to lysophospholipase, was incorporated in gpE, the lytic enhancement was not observed. The results of our experiments indicate that the membrane modulating effect of LL on lysis by C5b-9 requires the enzymatic breakdown of LL.