Can dose reduction be made in patients with allergic bronchopulmonary aspergillosis receiving high-dose omalizumab treatment?

Summary: Objective. To reduce the omalizumab dose in patients with allergic bronchopulmonary aspergillosis (ABPA) who were on long-term omalizumab treatment. Methods. Once asthma was controlled, two approaches were used to reduce total monthly omalizumab dose, 1) both extending dose intervals from 2 to 4 weeks and decrease omalizumab dose, 2) to reduce omalizumab dose while keeping dose intervals stable. Results. Thirteen patients with ABPA (8F/5M, mean age 53.4 ± 13.0 years) were included. Pre-omalizumab, mean blood eosinophil count was 723.1 ± 547.1 cells/mcL, mean numbers of attacks and hospitalizations were 2.5 ± 1.5 and 1.3 ± 0.8, respectively. Median total monthly omalizumab dose was 750 (min 300, max 900) mg. First and 2nd approach to reduce omalizumab dose was used in nine and four patients with a median time of reduction 32 (min 13, max 47) months. The 2nd dose reduction was made in four patients at median of 23.5 months. Pre-omalizumab, mean oral corticosteroid (OCS, as methylprednisolone) dose was 12.2 ± 10.4 mg daily, it decreased to 0.69 ± 0.95 mg (p = 0.001) in the 1st year of omalizumab and could be stopped in 11 patients. Attacks and hospitalizations decreased to 0.31 ± 0.86 (p less than 0.001) and 0 (p = 0.003), respectively, in the 1st year of omalizumab. Total omalizumab dose was reduced by median 40% (min 20, max 60) in 1st intervention and 50% (min 20, max 67) after 2nd intervention. After omalizumab reduction, asthma control did not deteriorate and there was no need to increase the omalizumab or OCS-dose. Conclusions. Decreasing the total omalizumab dose does not cause clinical deterioration in ABPA after the disease is controlled.

How do patients with asthma and COPD behave during fasting?

BACKGROUND-OBJECTIVE: Several factors might affect the adherence to treatment in patients with asthma and COPD. Among these factors, the effect of religious beliefs and behaviours has been less studied so far. In this study, the effect of fasting on drug use behaviours of patients with asthma and COPD were comparatively analysed. METHODS: A total of 150 adult patients with asthma and 150 adult patients with COPD were consecutively enrolled into this cross-sectional study. The patients were asked whether they fast during Ramadan and if the answer was yes, they were kindly asked to respond to further questions related to use of inhaled medications during that particular time. RESULTS: The majority of the cases from both groups [98 (65.3%) of asthma patients and 139 (92.6%) of COPD] were fasting during Ramadan. The majority of the patients with COPD (n=126; 90.6%) reported that they quitted their regular therapy basis during Ramadan. On the other hand, the majority of asthma patients used their controller inhaled medications during Ramadan and preferred to use them on iftar and sahur times (n=81, 82.6%). CONCLUSION: Our results showed that in a Muslim population, the patients with asthma and COPD do not feel their diseases to be an inhibitory factor for fasting during Ramadan. However, fasting seems to be an important determining factor in medication compliance by modifying the drug use behaviours in each group in a different way. Therefore, the patients should be informed about the effects of fasting on their disease and the allowed drugs during fasting.

Are drug provocation tests still necessary to test the safety of COX-2 inhibitors in patients with cross-reactive NSAID hypersensitivity?

Background: COX-2 inhibitors are safe alternatives in patients with cross-reactive non-steroidal anti-inflammatory drug (NSAID) hypersensitivity. These drugs are recommended to these patients after negative drug provocation tests (DPTs). However, cumulative data on encouraging results about the safety of COX-2 inhibitors in the majority of these patients bring the idea as to whether a DPT is always mandatory for introducing these drugs in all patients with cross-reactive NSAID hypersensitivity. Objective: To document the safety of COX-2 inhibitors currently available and to check whether or not any factor predicts a positive response. Methods: This study included the retrospective analysis of cases with cross-reactive NSAID hypersensitivity who underwent DPTs with COX-2 inhibitors in order to find safe alternatives. DPTs were single-blinded and placebo controlled. Results: The study group consisted of 309 patients. COX-2 inhibitors were well tolerated in the majority of the patients [nimesulide: 91.9%; meloxicam: 90.2%; rofecoxib: 94.9%; and celecoxib: 94.9%)]. Twenty-five patients (30 provocations) reacted to COX-2 inhibitors. None of the factors were found be associated with positive response. Conclusion: Our results suggest to follow the traditional DPT method to introduce COX-2 inhibitors for finding safe alternatives in all patients with cross-reactive NSAID hypersensitivity before prescription as uncertainty of any predictive factor for a positive response continues. However, these tests should be performed in hospital settings in which emergency equipment and experienced personnel are available (AU)

Are drug provocation tests still necessary to test the safety of COX-2 inhibitors in patients with cross-reactive NSAID hypersensitivity?

BACKGROUND: COX-2 inhibitors are safe alternatives in patients with cross-reactive non-steroidal anti-inflammatory drug (NSAID) hypersensitivity. These drugs are recommended to these patients after negative drug provocation tests (DPTs). However, cumulative data on encouraging results about the safety of COX-2 inhibitors in the majority of these patients bring the idea as to whether a DPT is always mandatory for introducing these drugs in all patients with cross-reactive NSAID hypersensitivity. OBJECTIVE: To document the safety of COX-2 inhibitors currently available and to check whether or not any factor predicts a positive response. METHODS: This study included the retrospective analysis of cases with cross-reactive NSAID hypersensitivity who underwent DPTs with COX-2 inhibitors in order to find safe alternatives. DPTs were single-blinded and placebo controlled. RESULTS: The study group consisted of 309 patients. COX-2 inhibitors were well tolerated in the majority of the patients [nimesulide: 91.9%; meloxicam: 90.2%; rofecoxib: 94.9%; and celecoxib: 94.9%)]. Twenty-five patients (30 provocations) reacted to COX-2 inhibitors. None of the factors were found be associated with positive response. CONCLUSION: Our results suggest to follow the traditional DPT method to introduce COX-2 inhibitors for finding safe alternatives in all patients with cross-reactive NSAID hypersensitivity before prescription as uncertainty of any predictive factor for a positive response continues. However, these tests should be performed in hospital settings in which emergency equipment and experienced personnel are available.

Triggers of asthma and COPD: are they different?

BACKGROUND: Asthma symptoms can be triggered by a variety of factors commonly referred to as "triggers". Some of these factors can also induce severe asthma exacerbations. Thus, it can be assumed that actions taken against such triggers may prevent the progression of the disease. However, limited data exist on the clinical importance of these triggers in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To compare the effect of triggers on symptoms and actions taken against certain modifiable triggers in patients with asthma and COPD. METHODS: The study was conducted in a university hospital between June 2009 and June 2010. Patients with asthma and COPD were asked to complete a questionnaire in which both the factors triggering symptoms and the actions taken against several triggers were assessed. RESULTS: Three hundred consecutive adult patients (150 asthma, 150 COPD) were enrolled to the study. The frequency of triggering factors was similar in both groups. Vaccination rates for influenza and pneumococcus were significantly higher in patients with COPD. However, such anti-allergic approaches as the use of strategies to decrease dust exposure, the use of anti-mite bed sheets, and the removal of pets from the home were more commonly employed by asthmatic patients. CONCLUSION: This study revealed that certain triggers affected COPD and asthma patients to the same degree. Therefore, triggers and strategies for controlling modifiable triggers should be more concentrated on during education in both groups. However, the preventive effect of these strategies on disease progression, particularly in patients with COPD, needs clarification.

Severity and associated risk factors in adult asthma patients in Turkey.

BACKGROUND: The prevalence of asthma of varying severity and associated risk factors are unknown in Turkey. OBJECTIVE: The study investigated the distribution of asthma severity, the factors having roles in asthma severity, and the relationship between serum eosinophil cationic protein (ECP) levels and disease severity. METHODS: Three hundred patients with asthma (73 male, 227 female) were enrolled in the study. The patients were surveyed for their smoking habits, educational levels, household incomes, asthma duration, occupations, and accompanying diseases. ECP levels were also determined in certain patients representing different disease severities (n: 76) and in a control group (n: 9). RESULTS: Patients were classified as mild intermittent (n: 14, 5%), mild persistent (n: 220, 73%), moderate (n: 44, 15%), and severe asthma (n: 22, 7%). Cigarette consumption and educational status were similar in all groups. A longer duration of disease and an older population predominated in patients with moderate and severe asthma. Analgesic sensitivity was seen in 7%, 10%, 6%, and 31% of mild intermittent, mild persistent, moderate and severe asthma patients, respectively, with the highest ratio in severe asthma (P < .05). Nasal polyps were significantly higher in severe asthmatics. Atopy was diagnosed in 85%, 57%, 56% and 10% of mild intermittent, mild persistent, moderate and severe asthma patients, respectively. ECP levels were significantly higher in moderate and severe asthma patients. CONCLUSIONS: Mild asthma was the most common clinical presentation and was associated with atopy. The factors associated with severe asthma included prolonged asthma duration, advanced age, nonatopy, analgesic intolerance and nasal polyps. ECP levels also reflected disease severity.

The use of nimesulide in patients with acetylsalicylic acid and nonsteroidal anti-inflammatory drug intolerance.

Intolerance or idiosyncrasy to acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs) is a crucial problem because these drugs are frequently used in medical treatment. In this study, we tested whether nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, might be a valid alternative for patients with histories of adverse reaction to ASA or NSAIDs. A single-blind, placebo-controlled oral challenge procedure was applied to 60 adult patients (19 male, 41 female; with a mean age of 40.31 +/- 10.44 years, range 20-68 years) with a reliable history of ASA/NSAIDs-intolerance. According to history, the clinical presentations of intolerance were urticaria/angioedema in 32 patients, anaphylactoid reaction in 2 patients, respiratory reaction in 19 patients, and respiratory and cutaneous reaction in 7 patients. Atopy was confirmed by means of skin prick test with inhalant allergens. Oral challenge protocol was started with 25 mg of nimesulide and the remaining 75 mg was given 1 hr later. During the challenge procedure, blood pressure, pulse, nasoocular, pulmonary, and cutaneous symptoms were monitored. Of the 60 patients tested, 55 (91.7%) tolerated the drug with no adverse reaction. Only five (8.3%) patients demonstrated a positive response to oral challenge. The clinical presentations of intolerance to nimesulide were urticaria/angioedema in three patients, mild rhinitis in one patient, and mild dyspnea in one patient. The atopy prevalence was higher, with a ratio of 41.7%, in patients with ASA/NSAIDs intolerance than that of the healthy adult population in Turkey (p < 0.05). We believe that nimesulide can be used as an alternative drug for patients with ASA/NSAIDs intolerance.

Bronchial hyperreactivity and immunoglobulin E in Behçet's disease.

Behçet's disease in a multisystem panvasculitis of unknown etiology. Pulmonary manifestations are rare, and there is no specific test to establish the inflammation for the precise differentiation between the active and inactive cases. Bronchial hyperreactivity (BHR) measured by methacholine challenge test and serum total IgE concentrations were investigated in 31 patients who were followed at Behçet's Center in hospital clinic and ten healthy controls. The patients studied had no evidence of neither any pulmonary disease-both allergic and nonallergic-nor family history of atopy. In 14 patients (45.16%) with active lesions mean IgE levels were higher than inactive group, 156.43 +/- 381.14 kU/L and 94.42 +/- 147.55 kU/L respectively (p > 0.05). We found high total IgE levels in eight patients (25.81%) with BD, though they were unrelated to disease activity. In our study, BHR related with Behçet's chronicity were also found to be positive in eight patients (25.81%). Mean time elapsed since the first diagnosis of the disease in patients with positive BHR was (11.13 +/- 3.72 years) significantly longer than inactive group (7.10 +/- 4.49 years) (p < 0.05). No correlation was found between BHR and serum IgE levels in patients with clinical symptoms. Therefore, we suggest that BHR may probably reflects nonspecific inflammation which is seen in BD, but cannot be regarded as a specific marker.

Effect of pretreatment with heparin on pulmonary and cutaneous response.

Although anticoagulant properties of glycosaminoglycan heparin are primary in medicine, a variety of other biological functions related to heparin have been suggested. Since heparin is a selective inhibitor of inositol triphosphate (IP3) receptors that are involved in release of calcium in mast cells and many other cells, it is possible that heparin may act as a natural anti-inflammatory molecule and modify these reactions. Therefore, the purpose of the present study was to determine the role of heparin in allergic inflammatory responses: the pulmonary reaction and the cutaneous response, in a double-blind, placebo-controlled, crossover randomized trial. To evaluate the effect of heparin on methacholine-induced bronchoconstriction, nebulized heparin (20,000 units) was administered to 12 asthmatics and nonspecific challenge was performed immediately thereafter. Measurements of Raw and SGaw were obtained before and 1 hr after nebulization of heparin. In 12 other allergic subjects, heparin (25 U/kg) was given intravenously 10 min before skin prick test. We demonstrated that pretreatment with heparin reduced skin test reactivity from 24.06 +/- 1.2 mm to 18.26 +/- 2.27 mm and increased the methacholine PC20 value from 1.69 +/- 0.48 mg/ml to 8.14 +/- 3.11 mg/ml (p < 0.05), but did not prevent an increase in Raw and/or a decrease in SGaw. Heparin modified the methacholine-induced bronchoconstrictor response, but this did not reflect a protective effect in airway resistance and specific conductance. These data suggest that anti-inflammatory effects of heparin are time-dependent and/or that heparin may have a transient inhibitory role in allergic reactions.

Evaluation of exposure to mite allergens; flotation, ELISA and Acarex comparative study.

House dust mites (HDM) are a major cause of allergic sensitization and airway disease. Technological advances in assays permit the measurement of major mite allergens in house dust samples more accurately. We compared the results of different methods in the assessment of exposure to domestic mites in sensitized patients. Three methods were used for mite assays on house dust samples: Mites were evaluated by microscope after flotation technique; major mite allergens. Der p l and Der f l, were determined by ELISA; the Acarex-Test was performed for the determination of guanine content. There was no significant difference between flotation and ELISA in the assessment of mite allergens. However, Acarex-Test was different from the other methods tested. being higher in skin test positive patients. We found a significant correlation between Der p l levels and mite specific immunoglobulin E determined by ELISA and CAP RAST respectively. Our findings show that mite determination by flotation method could be reinforced where the advanced methods are not available. Although the mite allergen levels measured in this study with various methods were not always in close association with house dust mite sensitization, the importance of mite-avoidance measure to house dust mites evaluated by skin tests and RAST should not be underestimated.

The effectiveness of benzyl benzoate and different chemicals as acaricides.

Several observations have indicated that house-dust mites (HDM) play an important role in allergic diseases. Thus, the primary form of treatment should aim at reducing exposure to HDM for these patients. Allergen-avoidance measures in homes have been demonstrated to be beneficial in decreasing the risk of sensitization, severity of symptoms, bronchial reactivity, and basophil sensitivity. Various chemical methods, as well as physical measures, have been tried to eliminate mite allergens from house dust. However, none have gained wide acceptance because of the lack of effectiveness and safety, and the high cost. It is clear that new approaches are required for effective long-term control of HDM allergens. This study compared the acaricidal activities of phenyl salicylate, tea leaf extract (high tannic acid content), and essential oils (eucalyptus and laurel) with that of benzyl benzoate. The contact, short-duration persistence, and residual effects of various concentrations of these chemicals and benzyl benzoate were assessed in laboratory conditions with specially designed wells. Our data suggest that benzyl benzoate may not be effective when applied according to the manufacturer's instructions, but may be effective when applied more frequently (i.e., three to four times a year) and for longer periods (up to 24 h) even with lower concentrations (0.4%). Essential oils were shown to have little acaricidal activity, but virtually no effect was observed with tea. Among the chemicals used, phenyl salicylate seems to be promising as an alternative acaricide.

The mechanism of bronchial hyperreactivity in allergic rhinitis patients. A light microscopic study on BAL and bronchial biopsy.

Epidemiological data indicated that allergic rhinitis often coexists with and may precede the development of reactive airway disease. In particular, ARP with BHR are more likely to develop asthma. However, the pathogenesis of BHR associated with allergic rhinitis is still remains uncertain. Therefore we designed the study on ARP with/without BHR. The aim of this study were to investigate the presence of an inflammatory process in lower respiratory tract in ARP and to relate these changes to airway responsiveness Eleven ARP with BHR (Group I), eleven ARP without BHR (Group II) and two control patients (Control group) were studied. All of the ARP were judged atopic on the basis of positive skin prick test to common inhalant allergens. Bronchial challenges were performed with increasing concentration of M. All the subjects underwent fiberoptic bronchoscopy, BAL and bronchial biopsies were obtained for pathologic examination. The mean total cell and the mean percentage of macrophages, lymphocytes, neutrophils and eosinophils in BAL fluid were in normal range in all groups without any significant differences between the groups. There weren't any correlation between PC20 to M and the total cell counts and percentage counts of these cells. In bronchial biopsy samples, the absolute numbers of lymphocytes, neutrophils, eosinophils and mast cells in the submucosa showed no differences between the three groups. The epithelial shedding was more extensive in ARP than control subjects (p = 0.05). The thickness of the epithelium was prominent in Group I (p < 0.05) but there was no significant differences in the basement membrane thickening between the three groups. We could only find an inverse correlation between PC20 to M and the mast cell counts in the submucosa (r xy:-0.815 p < 0.05). In conclusion, we couldn't observe any prominent morphological changes which indicate that may cause of BHR in ARP except the increased epithelial shedding in Group I. However, the increased epithelial shedding is not a reliable criterion to comment because of the possibility of mechanical damage of bronchial biopsies caused by the forceps.

Serum and pleural fluid selenium, copper, zinc, and magnesium levels in malignant and nonmalignant pleural diseases.

In the present study, selenium (Se), copper (Cu), zinc (Zn), and magnesium (Mg) levels in serum and pleural fluid from patients with malignant and nonmalignant pleural diseases were measured and compared with serum concentrations in healthy subjects. Serum/pleural fluid ratios were also calculated for each element. The purpose of this study was to evaluate the diagnostic value of trace metals, especially Se, in neoplastic and nonneoplastic pleural diseases. Serum Cu and Mg levels were significantly higher in both malignant and nonmalignant groups of patients when compared with control subjects (p < 0.05). However, serum levels of these elements did not show a significant difference between malignant and nonmalignant cases (p > 0.05). The serum/pleural fluid ratio of Zn was significantly lower in patients with malignant effusions than in benign conditions (p = 0.05). Serum and pleural fluid Se, Cu, Zn and Mg levels were not significantly different between the two groups (p > 0.05). Thus, Se, Cu, Zn, and Mg seem to have no diagnostic value for distinguishing malignant from nonmalignant effusions.

Increased chemotactic responses of neutrophils in intrinsic and mixed asthmatic patients.

Neutrophils are thought to contribute actively in the pathogenesis of asthma since they infiltrate into the lung tissue. The aim of this study is to compare the chemotactic responses of neutrophil granulocytes from 10 intrinsic, 13 extrinsic and 10 mixed type asthmatic patients with each other and chemotactic response of neutrophil granulocytes from 26 healthy individuals. All patients were free of infection and not receiving systemic corticosteroids. Significant differences were not found in random migration between all of the groups. However, chemotactic activity with zymosan activated serum was significantly elevated in intrinsic and mixed asthmatic patients (p < 0.001). In conclusion, the present investigation demonstrated increased chemotactic responses of neutrophils from asthmatic patients except extrinsic type.