Randomised trial comparing as-needed versus regular treatment with formoterol in patients with persistent asthma

PURPOSE: The aim of this study was to demonstrate the equivalent efficacy of inhaled formoterol in asthmatic patients, either given as-needed or on a regular twice-daily schedule. METHODS: Randomised, open 12-week study in patients with mild to moderate asthma not adequately controlled with inhaled glucocorticosteroids alone. Patients received inhaled formoterol as needed or on a regular schedule (2x2 puffs/day with 6 microg formoterol per puff). Patients in the twice-daily formoterol group could use salbutamol as a rescue medication. The primary endpoint was the number of patients with asthma exacerbations in each group. RESULTS: Thirty-nine centres randomised 359 patients. The number of patients with asthma exacerbations showed neither a clinically relevant nor a statistically significant difference between groups: formoterol as-needed: 3.95% (7 of 177); twice daily: 3.45% (6 of 174). Patients in the formoterol as-needed group used significantly less formoterol (-1.5 puffs per day; P<0.0001). Including the saved rescue medication (up to one puff per day), total beta-2 agonist use in the formoterol as-needed group decreased by approximately 2-2.5 puffs per day. Both formoterol treatment schedules were well tolerated. Musculoskeletal pain and tremor were less frequent in the formoterol as-needed group: headaches were slightly more frequent. CONCLUSION: Formoterol given as needed and without additional beta-2 agonist, and formoterol given on a regular basis twice daily, supplemented by salbutamol as a rescue medication, appeared equally effective in this clinical study. Drug consumption was markedly lower in the former group.     

Through the eyes of women: cultural insights into living as a battered woman in Hawaii

Abstract   This phenomenological study examined the impact of culture on the lived experience of women who were victims of intimate partner violence (IPV). The analysis of the data, using the method of Colaizzi, yielded three theme clusters: "living in misery", "enduring terror and sadness", and "no happy ending". They revealed the essential structure of living in a violent situation. The women, from diverse cultural backgrounds, had similar individual responses to violence. Although on a societal level, responses to violence are unique, the results revealed that women's responses were very personal and common across cultures, demonstrating their fundamental humanness. This finding underscores the importance of providing caring, individual support when working with victims of IPV, even though various cultures might perceive IPV differently. An ecological model for understanding the responses to IPV includes both individual and group perspectives related to IPV and the factors that influence the behavior of both women and men.     

Lung fibroblasts from patients with emphysema show a reduced proliferation rate in culture.

Emphysema is characterised by a loss of alveolar structure, as reflected in elastic recoil and gas exchange. As fibroblasts play a key role in the maintenance of structure, the current authors hypothesised that their proliferation might be constitutively impaired in lung emphysema. Using explant cultures, lung fibroblasts were obtained from resected lungs of 10 patients with emphysema (median forced expiratory volume in one second (FEV1) 40% predicted) and 10 control patients (FEV1, 95% pred). The doubling time (DT) was measured over 4 days under standard conditions (10% foetal calf serum) prior and after cryopreservation. Additionally, in seven samples per group the total population doubling level (PDL) was determined. In emphysema, mean+/-sem DT was 33.6+/-2.8 h compared with 24.8+/-1.4 h in controls. The differences in DT were preserved after cryopreservation. Groups also differed in the initial slope of the PDL plot during long-term culture (up to 35 days). However, the median (range) maximum PDL did not differ significantly between groups (13.8 (7.4-22.6) versus 20.2 (11.2-25.5)). The current authors, therefore, suggest that the reduced proliferation rate in vitro of lung fibroblasts from patients with emphysema reflects a persistent, intrinsic failure of cellular replacement and maintenance in this disease, possibly in relation to pre-term aging.     

Alveolar macrophages from bronchoalveolar lavage of patients with pulmonary histiocytosis X: Determination of phenotypic and functional changes

In recent years the alveolar macrophage has been found to play a central role in interstitial lung disease. Pulmonary histiocytosis X is characterized by infiltrating fibroblasts, mononuclear cells, and CD-1-positive Langerhans cells. Bronchoalveolar lavage (BAL) fluid displays an increase of CD-1-positive cells and a remarkable exaggeration of the total cell count with only slight changes in the differential cell count. Changes of alveolar macrophage phenotype and functional activity occurring in pulmonary histiocytosis X have not yet been characterized. The BAL fluid of nine patients with histologically proven isolated pulmonary histiocytosis X was compared with that of 16 control patients. Immunophenotyping of alveolar macrophages by monoclonal maturation and differentiation markers of monocyte/ macrophage lineage cells [Ki-M2, Ki-M6 (CD-68), Ki-M8, Ki-M1 (CD- 11c)] revealed a significant increase of immature macrophages with a more monocyte-like phenotype. The proliferation marker Ki-67 revealed an increased proportion of proliferating macrophages. Functional analysis by measuring oxygen radical release revealed an increase both in baseline and stimulated luminol-enhanced chemiluminescence. Fibronectin production was elevated in alveolar macrophage supernatants from pulmonary histiocytosis X patients. These findings are consistent with phenotypic changes of alveolar macrophages in other interstitial lung diseases such as sarcoidosis and idiopathic pulmonary fibrosis. Local proliferation and the fresh influx of blood monocytes seem to be responsible for the increase in immature and functionally activated alveolar macrophages. The increase in oxygen radical release and fibronectin production suggests an augmented tissue injuring and fibrosing capacity of alveolar macrophages in pulmonary histiocytosis X.     

Literature-based values of control subjects in sleep medicine

Summary Question of the Study To establish literature-based values of control subjects in sleep medicine. These data should give a range for the interpretation of polysomnographic results. Patients and methods We systematically collected and pooled data of control subjects in different sleep studies. We calculated the weighted arithmetical mean of these data, i. e. the mean of the means of multiple studies, with consideration being given to the number of the individual values concerned. Since the data in the literature were not presented uniformly, we were not able to establish standard deviations. Reported sleep stages were accepted only when the Rechtschaffen and Kales classification was applied. Arousals were accepted only if established in accordance with the criteria of the American Academy of Sleep Medicine. Whenever possible we calculated data broken down for age groups. Results Usable data were obtained from studies of between 10 and 1023 control subjects. The age range extended from infancy to 85 years. Data on sleep stages, sleep latencies, arousals, oxygen saturation, partial pressure of carbon dioxide, apneas and hypopneas were processed. Sleep latency and proportion of sleep stages are influenced by the first-night effect. Conclusions The data reflect the current status. When more control data are published the tables will have to be updated.     

Anaemia in pregnancy: Plasmodium falciparum infection is an important cause in primigravidae in Hoima district, western Uganda

Infection with Plasmodium falciparum is a major cause of anaemia in pregnancy, especially in primigravidae. Of 853 primigravidae visiting an antenatal clinic in Hoima district, western Uganda, for the first time, 530 (62.1%) were found to have P. falciparum parasitaemias and 305 (57.5%) of these had at least 1000 parasites/microliter blood. Plasmodium falciparum parasitaemia was significantly associated with anaemia (relative risk = 0.84, with 95% confidence limits = 0.74-0.96; P = 0.01). Malarial parasites were detected in > 80% of the women who had severe anaemia (P = 0.0008) and haemoglobin concentrations decreased with increasing intensity of infection (P = 0.03). Malarial hyper-reactive splenomegaly was associated with high parasite density (P = 0.01) and low haemoglobin level (P < 0.0001). Effective measures aimed at prevention of malaria and anaemia in pregnancy, especially in primigravidae, would significantly reduce anaemia and its deleterious effects on both the mother and the baby.     

Relationship between bronchoalveolar lavage neutrophil numbers and lavage fluid elastase and antielastase activities

Elastase and antielastase activities were measured in bronchoalveolar lavage fluid (BALF) and their relationship to bronchoalveolar lavage (BAL) neutrophil numbers was assessed in order to determine whether the elevated BAL neutrophil count can predict a shift in the elastase/antielastase balance. BAL samples were obtained from 133 randomly selected patients undergoing diagnostic bronchoscopy with BAL. Elastase and antielastase activities were determined using the synthetic substrate MeO-Suc-Ala-Ala-Pro-Val-pNA. In a random subset of 24 samples, the antioxidant capacity was measured as the inhibition of peroxyl radical-mediated oxidation of B-phycoerythrin. Only 7 of the BAL samples exhibited measurable elastase activity and all but one of these had a BAL neutrophil count greater than 100 × 103/ml. Antielastase activity was measurable in 124 samples exhibiting no free elastase activity. There was a tendency for lower antielastase activity to be associated with higher neutrophil numbers, but this did not translate into a statistically significant correlation over all samples. There was no significant correlation between antioxidant capacity and either the neutrophil number or antielastase activity. It is concluded that BAL neutrophil numbers do not, in general, predict the status of elastase/antielastase balance in the epithelial lining fluid and that the antioxidant mechanisms in the epithelial lining fluid do not appear to be related to the antielastase capacity.     

Montelukast attenuates the airway response to hypertonic saline in moderate-to-severe COPD.

This study assessed the effect of the leukotriene receptor antagonist montelukast on hypertonic saline-induced airway obstruction. A total of 29 patients with chronic obstructive pulmonary disease (forced expiratory volume in one second (FEV1), 42+/-4% predicted) received either 10 mg montelukast and 3 h later placebo via metered-dose inhaler (MDI) (M), or placebo and 3 h later 200 microg salbutamol (S), or two doses of placebo (P), in a randomised order. Patients inhaled salbutamol 1 h after MDI and the challenge was performed 15 min later (3% saline, 5 min). Data are given as per cent changes versus baseline. Compared to P, S caused significant bronchodilation in FEV1 (7.3%) and forced inspiratory volume in one second (FIV1) (4.5%), and M in FIV1 (1.5%). The saline-induced fall in FEV1 was lower after M (-5.8%), compared with S (-10.3%) and P (-13.1%). FEV1 (11.3%) and FIV1 (7.6%) was improved over baseline after recovery by M but not P and S. Recovery times regarding FEV1 (8.5 min) and FIV1 (15.2 min) were shortest after M, respective values for S being 16.8 and 20.4 min, and for P 15.9 and 21.2 min. Effects were strongest in patients with low baseline FEV1 and/or inhaled corticosteroids. Data from this study indicate beneficial effects of montelukast on hypertonic saline-induced airway responses in patients with chronic obstructive pulmonary disease, particularly those with severe disease. The major effect was an accelerated recovery leading to values above baseline.