The bronchoprotective effect of inhaled salmeterol in preschool children: a dose-ranging study.

The optimal dose of salmeterol in infants and preschool children is not known. The aim of this study was to assess the bronchoprotective effect of different doses of salmeterol using methacholine-induced wheeze in children aged <4 yrs. Children <4 yrs old with a history of recurrent wheeze underwent two methacholine challenges within 7 days. One hour before each challenge they were pretreated in double-blind fashion using a metered-dose inhaler and Babyhaler spacer. Placebo was given before one challenge, and either 25, 50 or 100 microg of salmeterol before the other. Both the dose and treatment order were random. The provocative concentration of methacholine causing wheeze (PCwheeze) was measured on each occasion. Studies were terminated when wheeze occurred or arterial oxygen saturation (Sa,o2) fell below 91%. Of the 42 children enrolled, 33 completed the study. Two subjects refused the challenge test, two failed to return and five developed upper respiratory tract infections or wheeze between the two tests. The mean (range) age of the population was 27 (8-46) months. Ratios of PCwheeze between treatment and placebo challenges were calculated for each dosage group. The treatment/placebo ratios (95% confidence intervals) were 1.2 (0.6-2.4) for 25 microg, 2.5 (1.4-4.6) for 50 microg (p<0.01), and 4.0 (2.1-7.4) (p<0.001) for 100 microg doses. In recurrently wheezy children aged <4 yrs a single dose of salmeterol between 25 and 100 microg has a dose-dependent effect on methacholine-induced wheeze, and this is significantly different from placebo at 50 and 100 microg. This study suggests that the Babyhaler effectively delivers salmeterol to children <4 yrs of age and that doses between 50-100 microg are efficacious.     

First experience of SARS‐CoV‐2 infections in solid organ transplant recipients in the Swiss Transplant Cohort Study

Immunocompromised patients may be at increased risk for complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, comprehensive data of SARS‐CoV‐2 infection in solid organ transplant (SOT) recipients are still lacking. We performed a multicenter nationwide observational study within the Swiss Transplant Cohort Study (STCS) to describe the epidemiology, clinical presentation, treatment and outcomes of the first microbiologically documented SARS‐CoV‐2 infection among SOT recipients. Overall, 21 patients were included with a median age of 56 years (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations). The most common presenting symptoms were fever (76%), dry cough (57%), nausea (33%), and diarrhea (33%). Ninety‐five percent and 24% of patients required hospital and ICU admission, respectively, and 19% were intubated. After a median of 33 days of follow‐up, 16 patients were discharged, 3 were still hospitalized and 2 patients died. These data suggest that clinical manifestations of SARS‐CoV‐2 infection in middle‐aged SOT recipients appear to be similar to the general population without an apparent higher rate of complications. These results need to be confirmed in larger cohorts.     

The effect of supplementary oral nutrition in poorly nourished patients with chronic obstructive pulmonary disease

We carried out a prospective, randomized, controlled trial to investigate the effect of a 3-month period of supplementary oral nutrition in 14 poorly nourished outpatients with COPD. Seven patients were randomized into Group 1 who received their normal diet during Months 1 to 3, a supplemented diet during Months 4 to 6, and their original normal diet during Months 7 to 9. The other 7 patients received their normal diet for the entire 9-month study period (Group 2). Seven well-nourished patients (Group 3) matched for age and severity of air-flow obstruction served as control subjects; they received their normal diet for the 9-month study period. Measurements of nutritional status, respiratory muscle and handgrip strength, sternomastoid muscle function (including frequency/force curves, maximal relaxation rate, and a fatigability test), lung function, arterial blood gas tensions, general well-being and breathlessness scores, and 6-min walking distances were carried out monthly in all patients. At the start of the study, the poorly nourished patients had lower mean daily calorie and protein intakes than did the well-nourished patients. The poorly nourished patients had lower respiratory muscle and handgrip strength, and abnormal contractility and increased fatigability of the sternomastoid muscle compared with those in the well-nourished patients. After 3 months of supplementary oral nutrition, there was a significant improvement in the nutritional status of Group 1 patients, as evidenced by an increase in body weight, triceps skinfold thickness, and midarm muscle circumference. Respiratory muscle and handgrip strength increased in parallel with nutritional status, although there were no significant changes in lung function or arterial blood gas tensions.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of low frequency fatigue on endurance exercise in the sternomastoid muscle of normal humans

It is not certain to what extent low frequency fatigue affects the performance of a muscle. We studied the endurance capacity of the sternomastoid muscle to undergo repetitive isometric neck flexion contractions for 2 s every 4 s at 35% of its maximal voluntary contraction force (MVC) in 5 normal subjects starting with different levels of fatigue. The endurance time, the duration the subjects were able to achieve the target force before exhaustion, was measured in each subject on 3 occasions: Study 1: in the fresh state, with a normal frequency/force curve and 20:50 ratio (ratio of force response at 20 Hz to that at 50 Hz) before the start of the endurance exercise; Study 2: with a moderately reduced 20:50 ratio before the start of endurance exercise (mean +/- SEM reduction in 20:50 ratio 11.4 +/- 0.8%); Study 3: with a substantially reduced 20:50 ratio before the start of the endurance exercise (29.2 +/- 3.7%). These reductions in 20:50 ratio were produced by the subjects performing 150 isometric neck flexion contractions at 50% of their MVC, followed by a period of rest to allow the 20:50 ratio to recover to approximately 10% of the starting value in Study 2, and to within 20 to 40% of the starting value in Study 3. Endurance exercise was then carried out.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diaphragm paralysis causing ventilatory failure in an adult with the rigid spine syndrome

A syndrome consisting of a rigid spine and myopathy predominantly affecting proximal limb muscles has been previously described in children, and as with most neuromuscular disorders, the respiratory muscles appear to be affected only at an advanced stage in the disease. We describe an adult male with this syndrome who presented with ventilatory failure caused by severe respiratory muscle weakness and who demonstrated profound nocturnal arterial oxygen desaturation, particularly during rapid eye movement sleep. Treatment with negative pressure ventilation initially resulted in only modest improvements in symptoms, blood gas tensions, and nocturnal desaturation. The cause of this only partial improvement was upper airway obstruction provoked by the mode of ventilatory support used. After tracheostomy there was a dramatic and sustained improvement in symptoms and blood gas tensions and complete abolition of nocturnal arterial oxygen desaturation. This is the first report of an adult with the rigid spine syndrome presenting with ventilatory failure and cor pulmonale due to severe respiratory muscle weakness.     

A dose escalation study of docetaxel plus capecitabine in combination with gemcitabine in patients with advanced solid tumors

Capecitabine (CAP), gemcitabine (GEM), and docetaxel (DOC) have shown interesting activity in a wide range of solid tumors. A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of their combination in patients with refractory solid tumors. Eighteen patients were enrolled. The patients' median age was 60 years, 15 were male, and 11 were chemo-naive. DOC was administered on day 1 as an 1-h (IV) infusion at escalating doses ranging from 40 to 50 mg/m2. GEM was administered on day 1 as a 30-min (IV) infusion at a standard dose of 1500 mg/m2. CAP was administered orally on days 1 to 7 at escalating doses ranging from 1750 to 2500 mg/m2 given as two daily divided doses. Treatment was repeated every 2 weeks. Five different dose levels were examined. At dose level V two out of three enrolled patients presented DLTs (one patient grade 4 neutropenia and grade 3 stomatitis and another grade 3 diarrhea), and thus the recommended MTD for future phase II studies are CAP 2250 mg/m2, DOC 50 mg/m2, and GEM 1500 mg/m2. A total of 124 treatment cycles were administered. Toxicity was generally mild. Grade 3/4 neutropenia was observed in eight (7%) treatment cycles and grade 3 thrombocytopenia in one (1%). There was no febrile episode. Grade 2/3 asthenia was observed in six (33%) patients, grade 2/3 diarrhea in four (22%), and grade 2/3 hand-foot syndrome in three (17%). Other toxicities were uncommon. There was no treatment-related death. One (6%) CR, four (25%) PRs, and six (38%) SD were observed among 16 evaluable patients. Responses were seen in patients with breast (one CR), gastric (three PRs), and pancreatic (one PR) cancer. These results demonstrate that CAP, DOC, and GEM can be safely combined at clinically relevant doses and this regimen merits further evaluation.     

Evaluating the effects of asthma therapy on childhood growth: what can be learnt from the published literature?

The difficulties of assessing the effects of asthma therapy on childhood growth were explored in the first part of this review. In this part of the review growth studies with inhaled corticosteroids were selected that included a control group, measured height by stadiometry and were of > or = 1 yr duration. The studies were classified as type 1 (placebo control), type 2 (nonsteroidal therapy control), type 3 (comparator inhaled corticosteroid control) or type 4 ("real-life" studies with dose adjustment). The design attributes of these studies were then compared with the recommendations described in the first part of this review. Of the 18 studies identified, 17 were susceptible to one or more important confounding factors. Nevertheless, the outcomes of all 18 studies were mostly consistent. At recommended doses, beclomethasone dipropionate and budesonide demonstrated a small degree of growth suppression over 1-2 yrs (study types 1 and 2), but there was little evidence of such an effect with fluticasone propionate. Studies comparing different inhaled corticosteroids at recommended doses indicated more rapid growth with fluticasone propionate than with beclomethasone dipropionate or budesonide. However, none of the inhaled corticosteroids appeared to affect final height. In conclusion, the results from the majority of published growth studies with inhaled corticosteroids must be interpreted with a degree of caution owing to their potential susceptibility to important confounding factors. Further well-designed studies are needed to establish whether different inhaled corticosteroids have different effects on growth in the long term.     

Importance of viruses and Legionella pneumophila in respiratory exacerbations of young adults with cystic fibrosis.

From January to April 1980 46 young adults with cystic fibrosis were studied for evidence of infection with a wide variety of microorganisms, including viruses and Legionella pneumophila. Two groups of patients were investigated: a "deteriorated" group of 24 patients who had experienced an increase in lower respiratory tract symptoms and fall in lung function values in the course of one month before the start of the study and a "stable" group of 22 patients with no such deterioration. All serological tests were repeated at one month and then one year after the beginning of the study. A fourfold rise in titres of antibodies to various viruses, Mycoplasma pneumoniae, and Coxiella burnetii was obtained in seven (29%) of the deteriorated group but in only one (4.5%) of the stable group (p less than 0.05). One other patient showed a fourfold rise in L pneumophila antibody titre (on the basis of the indirect fluorescent antibody test), which was accompanied by a respiratory illness consistent with legionnaires' disease. Eight of the 46 patients (17.4%) had demonstrable titres of antibody against L pneumophila (1/32 or above).