A randomized, double‐blind trial of the effect of glucocorticoid, antileukotriene and bβ‐agonist treatment on IL‐10 serum levels in children with asthma

BACKGROUND: Levels of an immunoregulatory and anti-inflammatory cytokine IL-10 are reduced in asthmatic airways, potentially contributing to more intense inflammation. Triamcinolone has anti-inflammatory properties and the anti-inflammatory effects of montelukast and formoterol have been discussed. OBJECTIVE: The purpose of this study was to define the effect of treatment with triamcinolone, montelukast and formoterol on the serum level of IL-10, eosinophil blood counts, eosinophil cationic response (ECP) and clinical parameters (symptom score, FEV1 and PC20H) in children with moderate asthma. METHODS: An 8-week, placebo-controlled and randomized, double-blind trial was carried out. The subjects were 91 children with moderate atopic asthma who were allergic to dust mite. Patients were randomly allocated to receive 400 microg triamcinolone (n = 19), 5 or 10 mg (according to age) montelukast (n = 18), 24 microg formoterol (n = 18) or placebo (n = 36). RESULTS: Seventy-nine children completed the study. After treatment with triamcinolone and montelukast the level of IL-10 in blood serum significantly increased, eosinophil blood counts and ECP levels significantly decreased and all clinical parameters improved; treatment with formoterol had no effect on IL-10 level, eosinophil blood counts in serum and bronchial hyper-reactivity; ECP level significantly decreased after treatment and asthma symptoms and FEV1 improved significantly. Mean IL-10 levels in serum before and after treatment with triamcinolone were 7.23 pg/mL with 95% CI, 6.74 -7.72% and 14.24 pg/mL with 95% CI, 11.6-16.88%, respectively (P < 0.001); with montelukast they were 6.59 pg/mL with 95% CI, 6.26-7.23% and 10.94 pg/mL with 95% CI, 8.24-12.65%, respectively (P < 0.002); with formoterol they were 7.06 pg/mL with 95% CI, 6.61-7.52% and 7.04 pg/mL with 95% CI, 6.15-7.93%. We found statistically significant correlations between serum level of IL-10 and serum level of ECP after treatment with triamcinolone and montelukast. CONCLUSION: This study demonstrates that one possible way by which triamcinolone and montelukast contribute to inhibition of inflammation is by increasing IL-10 levels.     

Validation of the Brazilian-Portuguese Version of the European Community Respiratory Health Survey in Asthma Patients

Background. The European Community Respiratory Health Survey (ECRHS) questionnaire was planned to answer questions about the distribution of asthma. Our objective was to determine the cultural equivalence of the ECRHS into the Brazilian-Portuguese language. Methods. We translated the ECRHS according to international criteria. Results. Small cultural adaptations were necessary. Among the 80 participating patients, the Cronbach indices were higher (0.98-1.00) and the Kappa indices varied from 0.77 to 1.00. Conclusion. The study suggests that the Brazilian version of the ECRHS is conceptually equivalent to the original and similarly reliable and may be used in international studies involving Portuguese-speaking respiratory patients.     

Uveal effusion syndrome

The history and clinical findings are presented of a patient who suffered from the uveal effusion syndrome over a 10-year period from 1956. The funduscopic appearance is illustrated both at the time of initial presentation and 36 years later. This condition typically affects healthy middle-aged men and causes recurrent, spontaneous, serous retinal and ciliochoroidal detachments, often resulting in significant visual impairment. Two separate hypotheses have been postulated to explain the pathogenesis of the uveal effusion syndrome, one relating to abnormally thickened sclera, the other to chronic bulbar hypotony. Both are discussed, as is the rationale behind the current management of this unusual condition.     

Risk factors for asthma in children in Lódź region

The incidence of asthma and other allergic diseases continues to increase. In addition to genetic factors, environmental influences are thought to play an important role. The aim of this study was to identify factors that influence and drive the atopic march from atopic sensitization to asthma in children from Lód?. METHODS: 800 atopic children, aged 5-18 years, were included to our study. Parents filled in questionnaires and gave interviews about their children's diseases. 405 (43%) children have diagnosis of asthma. RESULTS: A significant association was observed between asthma and male sex, parents' history of atopy, parental highest school grade, maternal smoking during pregnancy, maternal chronic disease (especially chronic renal diseases), maternal allergen-sensitizing diet during breast-feeding, increased exposure to indoor humidity and moulds. Similar effect was seen for episodes of wheeze occurring in the first 3 years of life as followed: wheezing during an airway infection, wheezing not connected with respiratory tract infection, wheezing not related with physical exercise. Child's daycare attendance (nursery school) was associated with decreased risk of asthma.     

Reach to grasp: the natural response to perturbation of object size

This study assessed the reach to grasp movement and its adaptive response to a perturbation of object size. In blocked trials, subjects (n = 12) were instructed to reach 35 cm to grasp and lift a small- (0.7 cm) or large-diameter (8 cm) cylinder. Under an unconstrained condition (condition 1), no instructions as to the type of grasp to adopt were given. Subjects thus naturally used a precision grip (PG) for the small cylinder and whole hand prehension (WHP) for the large cylinder. Under condition 2, subjects were instructed to utilize a PG for grasps of both the large and small cylinders. For condition 3, the instruction was to use WHP irrespective of object size. Kinematic organization was determined with analysis of the recordings of active markers placed on the wrist, thumb, and three fingers. For condition 1 the results showed a temporal arrangement of both components (transport and manipulation) which differed from that of conditions 2 and 3. In perturbed trials, illumination shifted from the small to large cylinder or vice versa. With condition 1, subjects automatically switched from one grasp to another with no or little increase of movement duration. This was generally achieved by an earlier temporal setting of peak wrist deceleration. For conditions 2 and 3, where a change of aperture was required, movement duration was prolonged without adaptation of earlier transport component parameters. It is concluded that the adaptive responses to a change of distal patterning also affect the organization of the proximal component. Assessment of grasps constrained by instructions may lead to interpretations of central control of the reach to grasp movement which differ from those obtained by assessing more natural prehensile patterns.     

P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens.

BACKGROUND: The prognostic and predictive value of cell cycle regulatory proteins in ovarian cancer has not been established. We evaluated the clinical and biological significance of P21(WAF1), P27(KIP1), C-MYC, TP53 and Ki67 expressions in ovarian cancer patients. MATERIALS AND METHODS: Immunohistochemical analysis was performed on 204 ovarian carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IV treated with platinum-based chemotherapy. Multivariate analysis with Cox and logistic regression models was performed in the whole group, and in the TP53-negative and TP53-positive subgroups. RESULTS: High P21(WAF1) labeling index (LI) was an independent positive predictor of platinum-sensitive response (P = 0.02). Overall survival was positively influenced by P21(WAF1) LI (P = 0.02) or by P21(WAF1) plus P27(KIP1) LI (P = 0.004) in the TP53-negative group only. Ki67 LI showed borderline association with disease-free survival (P = 0.05). Growth fraction was negatively associated with P21(WAF1) and P27(KIP1) indices in the TP53-negative group (P = 0.023 and 0.008, respectively), and these associations were borderline or lost in the TP53-positive group. Endometrioid and clear cell carcinomas differed from other carcinomas by having a low incidence of TP53 accumulation, a high incidence of C-MYC overexpression (70%) and a low median Ki67 LI (all with P <0.001). CONCLUSIONS: We have shown an independent predictive value of P21(WAF1) LI in ovarian carcinoma patients. The prognostic value of P21(WAF1) and P21(WAF1) plus P27(KIP1) LI was determined by TP53 status. A high frequency of C-MYC overexpression in endometrioid and clear cell carcinomas may suggest its role in the development of these tumor types.     

Transforming growth factor-beta1 and IL-13 response to allergen predict steroid needs in asthmatic children

BackgroundThe remission of asthma, which is induced during specific immunotherapy (SIT) or appears spontaneously in children is not completely understood and predictors of this phenomenon are still undefined.ObjectiveTo assess CD4⁺CD25⁺Foxp3⁺ Treg cells and cytokine/proliferation response to allergen-specific stimulation of PBMC as predictors of steroid sparing effect of SIT and steroid dosage needs without SIT during 5 years of follow-up in asthmatic children.MethodsThis is a 5-year long study of 32 asthmatic children, sensitive only to house dust mite (HDM). Eighteen children who had completed 5 years of HDM SIT – SIT group, and 14 children without SIT as a control group were studied. All patients had baseline clinical/immunological assessment; before and after observation the minimum effective ICS dose was defined and lung function was measured.ResultsIn children from SIT group minimum effective ICS dose was reduced more than in children from control group (median reduction 65% vs. 0%; p < 0.001). Among patients in control group asthma severity was reduced after 5 years of observation in those who had at baseline higher TGF-beta1 and lower IL-13 answer to allergen stimulation of PBMC. Better response to 5 years immunotherapy was observed in those who had at baseline higher TGF-beta1 and lower proliferation answer to allergen stimulation of PBMC.ConclusionSimilar processes may decide on both, SIT-induced and spontaneously appearing, reduction in asthma severity. Immunotherapy was much more effective than pharmacotherapy in our study. IL-13 overproduction may impede reduction of disease severity in asthmatic children independently from TGF-beta pathway.     

Efficacy and safety of the single-capsule combination of fluticasone/formoterol in patients with persistent asthma: a non-inferiority trial

OBJECTIVE:

Fluticasone and formoterol are effective in the treatment of asthma. When a corticosteroid alone fails to control asthma, combination therapy is the treatment of choice. The objective of this study was to compare the efficacy and safety of formulations containing budesonide/formoterol (BUD/FOR), fluticasone alone (FLU), and the single-capsule combination of fluticasone/formoterol (FLU/FOR) on lung function in patients with mild-to-moderate persistent asthma.

METHODS:

This was a randomized, multicenter, open phase III trial conducted in Brazil. The primary efficacy analysis was the assessment of non-inferiority between FLU/FOR and BUD/FOR combinations regarding FEV₁ (in L) at the final visit. The secondary analyses were PEF, level of asthma control, serum cortisol levels, frequency of adverse events, adherence to treatment, and appropriate inhaler use.

RESULTS:

We randomized 243 patients to three groups: FLU/FOR (n = 79), BUD/FOR (n = 83), and FLU (n = 81). In terms of the mean FEV₁ after 12 weeks of treatment, the difference between the FLU/FOR and BUD/FOR groups was 0.22 L (95% CI: −0.06 to 0.49), whereas the difference between the FLU/FOR and FLU groups was 0.26 L (95% CI: −0.002 to 0.52). Non-inferiority was demonstrated by the difference between the lower limits of the two 95% CIs (−0.06 vs. −0.002). The level of asthma control and PEF were significantly greater in the FLU/FOR and BUD/FOR groups than in the FLU group. There were no significant differences among the groups regarding patient adherence, patient inhaler use, or safety profile of the formulations.

CONCLUSIONS:

The single-capsule combination of FLU/FOR showed non-inferiority to the BUD/FOR and FLU formulations regarding efficacy and safety, making it a new treatment option for persistent asthma.     

Detection ofPneumocystis carinii with direct fluorescence antibody and calcofluor white stain

Summary Direct fluorescence monoclonal antibody stain (DFA) was compared prospectively, with calcofluor white (CFW) stain for the diagnosis ofPneumocystis carinii in 163 respiratory specimens from 97 patients. The patient population included persons with HIV infection (58%), bone marrow transplant recipients (10%), immunosuppressed patients owing to chemotherapy (21%) and others (11%). Nineteen specimens including 12 sputa, six bronchoalveolar lavage fluids (BALs) and one induced sputum were positive by DFA. In contrast, only six sputa, and five BALs were positive by CFW. All specimens positive by CFW were also positive by DFA. Of 86 sputa that were negative by either method 29 were followed by more invasive sample collections. Three specimens were followed by induced sputum collection, 18 by BAL, six by lung biopsy, and two by pleural fluid aspiration. All the subsequent induced sputa, pleural fluids, and lung biopsies were negative by both methods. However, four of 18 subsequent BALs (22%) were positive by both methods, provided at least two CFW stained slides were examined per specimen. Except for expectorated sputum, it is concluded that CFW is a rapid and inexpensive test to detectP. carinii in most respiratory specimens.

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Nachweis vonPneumocystis carinii mit direkter Antikörper-Fluoreszenztechnik (DFA) und Calcofluor Weiß-Färbung

Zusammenfassung Im prospektiven Vergleich wurde die diagnostische Aussagekraft der direkten Antikörper-Fluoreszenz-Technik und der Calcofluor-Weiß (CFW)-Färbung zum Nachweis vonPneumocystis carinii in 163 Proben aus dem unteren Respirationstrakt von 97 Patienten geprüft. Die Gruppe setzte sich aus Patienten mit HIV-Infektion (58%), Knochenmarktransplantations-Empfängern (10%), nach Chemotherapie immunsupprimierten Patienten (21%) und anderen (11%) zusammen. Mit DFA-Technik waren 19 Proben positiv; darunter waren 12 Sputumproben, sechs bronchoalveoläre Lavage (BAL)-Flüssigkeiten und ein induziertes Sputum. Mit CFW-Färbung waren sechs Sputumproben und fünf BAL-Proben positiv. Alle mit CFW positiven Proben waren auch mit DFA positiv. Eine erneute Probenahme mit invasiveren Methoden erfolgte in 29 von 86 mit beiden Nachweis-Verfahren negativen Fällen. In drei Fällen wurde induziertes Sputum gewonnen, in 18 Fällen eine BAL, in sechs Fällen eine Lungenbiopsie und in zwei Fällen eine Pleurapunktion durchgeführt. Alle in der Folge gewonnenen induzierten Sputa, Pleuraflüssigkeiten und Lungenbiopsien waren mit beiden Methoden negativ. Doch in vier der 18 BAL-Flüssigkeiten (22%) wurdeP. carinii nachgewiesen, dabei waren mindestens zwei mit CFW gefärbte Ausstriche pro Probe untersucht worden. Mit Ausnahme von Spontansputum eignet sich die CFW-Färbung als einfaches und billiges Verfahren bei den meisten Proben aus den tiefen Atemwegen zum Nachweis vonP. carinii.