Introduction and objectives Mycobacterium tuberculosis (MTB) emerged as a pathogen in Africa and has co-evolved with humans following the migration to Europe and Asia some 70,000 years ago. Distinct phylogenetic lineages of MTB associate with hosts of particular genetic ancestry, both in their regions of origin and in distant cosmopolitan urban settings where human populations of different ancestry intermingle. These different strains induce distinct patterns of cytokine and chemokine secretion (‘inflammatory profiles’) in human macrophages. Circulating and antigen-stimulated inflammatory profiles might therefore be expected to vary significantly between tuberculosis patients of different ethnic origin. We therefore conducted a study to determine whether such variation exists. Methods We measured circulating and antigen-stimulated concentrations of 43 soluble inflammatory mediators and 14 haematological parameters in 45 patients of African ancestry and 83 patients of Eurasian ancestry receiving intensive-phase antimicrobial therapy for smear-positive pulmonary tuberculosis in London, UK. Host and bacillary genotypes were also determined. Statistical analyses were performed to compare inflammatory profiles in patients of African vs Eurasian ancestry; to investigate the influence of host and bacillary genotype on inflammatory profile; and to determine immunological correlates of speed of elimination of MTB from sputum. Results Tuberculosis patients of African vs Eurasian ancestry had similar clinical characteristics, but exhibited distinct inflammatory profiles. Patients of African ancestry had lower neutrophil counts, lower serum concentrations of CCL2, CCL11 and vitamin D binding protein (DBP), and lower antigen-stimulated CCL11 secretion than those of Eurasian ancestry, but higher serum CCL5 concentrations and higher antigen-stimulated interleukin 1 receptor antagonist and IL-12 secretion. These differences did not relate to MTB strain variation between groups, but they did associate with ethnic variation in host DBP genotype. Ethnic differences in inflammatory profile became more marked following initiation of antimicrobial therapy, and immunological correlates of speed of elimination of MTB from the sputum were distinct for patients of African vs. Eurasian ancestry. Conclusions Our study demonstrates a hitherto unappreciated degree of ethnic heterogeneity in inflammatory profile in tuberculosis patients. Candidate immunodiagnostics and immunological biomarkers of response to antimicrobial therapy should therefore be derived and validated in tuberculosis patients of different ethnic origin.

SETTING Newham Chest Clinic, London, UK. OBJECTIVE To determine the safety and efficacy of the administration of bolus-dose vitamin D(2) in elevating serum 25-hydroxyvitamin D (25[OH]D) concentrations in tuberculosis (TB) patients. DESIGN A multi-ethnic cohort of TB patients was randomised to receive a single oral dose of 2.5 mg vitamin D(2) (n = 11) or placebo (n = 14). Serum 25(OH)D and corrected calcium concentrations were determined at baseline and 1 week and 8 weeks post-dose, and compared to those of a multi-ethnic cohort of 56 healthy adults receiving an identical dose of vitamin D(2). RESULTS Hypovitaminosis D (serum 25[OH]D < 75 nmol/l) was present in all patients at baseline. A single oral dose of 2.5 mg vitamin D2 corrected hypovitaminosis D in all patients in the intervention arm of the study at 1 week post-dose, and induced a 109.5 nmol/l mean increase in their serum 25(OH)D concentration. Hypovitaminosis D recurred in 10/11 patients at 8 weeks post-dose. No patient receiving vitamin D(2) experienced hypercalcaemia. Patients receiving 2.5 mg vitamin D(2) experienced a greater mean increase in serum 25(OH)D at 1 week post-dose than healthy adults receiving 2.5 mg vitamin D(2). CONCLUSION A single oral dose of 2.5 mg vitamin D(2) corrects hypovitaminosis D at 1 week but not at 8 weeks post-dose in TB patients.

Introduction: Vitamin D was used to treat tuberculosis (TB) in the pre-antibiotic era. Calcitriol, its active metabolite, restricts growth of M. tuberculosis in macrophages in vitro. We present results of the first clinical trial to investigate the effect of in vivo vitamin D supplementation on antimycobacterial immunity.

1. The rates of change in mean peak expiratory flow and in diurnal variation in peak flow were compared in 14 patients recovering from acute severe asthma. 2. Peak expiratory flow was measured on hospital admission, and at 6-hourly intervals for the next 3 weeks. 3. Diurnal variation in peak flow was assessed by measuring the following: amplitude (the highest minus the lowest peak expiratory flow during any given 24 h period), amplitude % mean (the highest minus the lowest peak expiratory flow during any given 24 h period divided by the mean peak expiratory flow over that period) and residual amplitude (the maximum variation about the mean peak expiratory flow during any given 24 h period). 4. Plots of diurnal variation in peak flow and peak expiratory flow against time were constructed for each patient. To enable comparison of changes in peak expiratory flow and diurnal variation in peak flow the data were transformed. 5. The rate of change for mean peak expiratory flow and for the three measures of diurnal variation in peak flow was assessed by fitting an exponential function to each set of data, and calculating the slope of the exponential curve halfway through the period of observation (10.5 days). 6. Median (range) slope for peak expiratory flow was 0.055 (0-2.57). The comparable value for amplitude was -3.15 (-1.27 to -4.22) (absolute median values compared, P = 0.0029), for amplitude % mean was -1.87 (-0.18 to -5.95) (P = 0.012) and for residual amplitude was -1.43 (-0.62 to -3.09) (P = 0.033).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in spirometry during consecutive admissions for treatment of pulmonary infective exacerbations were studied in 45 patients (24 males, 21 females) with cystic fibrosis (CF) who had required five or more such admissions. Over the overall study period there was a mean (SD) decline in FEV1 of -112.1 (188.0) ml yr-1 (P less than 0.001) and in FVC of -47.9 (82.4) ml yr-1 (P less than 0.001). FEV1 and FVC increased during each admission with treatment; however, the magnitude of this change became less over consecutive admissions by a mean value of -33.3 ml (45.0) (P less than 0.001) for FEV1, and -26.0 (72.2) ml (P less than 0.05) for FVC. In the majority of patients that died or underwent transplantation, FEV1 at the time of the last admission did not rise above 800 ml despite full treatment.

Nocturnal symptoms are common and often disabling in asthmatic subjects. Furthermore, they often persist, in spite of appropriate dosages of inhaled beta-2-agonists and topical steroids. In such a clinical situation, theophylline preparations may have a therapeutic role. This double-blind, placebo-controlled, cross-over trial was designed to evaluate the effectiveness of a twice-daily Bioavail slow-release theophylline capsule in a group of out-patient asthmatics, with a history of nocturnal and/or early morning wheeze or chest tightness. Theophylline was initially prescribed and monitored in an 'open' phase to obtain the drug dosage required to achieve a serum level in the therapeutic range of 10-20 mg/l. In the ten patients who completed the study, serum theophylline levels were stable throughout.During active treatment there was an improvement in morning peak expiratory flow rate (PEFR), and a reduction in measurements of diurnal variation. In addition, the bronchodilator response to an inhaled beta-2-agonist was preserved. Bioavail theophylline has thus been shown to be an effective agent in the management of adults with nocturnal asthma.

The effect of exercise on gas exchange was studied in 17 patients (seven male and 10 female) recovering in hospital from acute severe asthma. On admission the patients (mean age 26 (SD 8) years) had a mean peak expiratory flow (PEF) of 26.8% (5.7%) predicted, a mean arterial oxygen tension (PaO2) of 8.63 (1.26) kPa, and a mean alveolar-arterial oxygen difference (A-aDO2) of 5.98 (1.34) kPa. Once resting symptoms had resolved (after 3.7 (1.6) days) patients performed a constant load exercise test (100 watts for men, 75 watts for women) on a bicycle ergometer for five minutes. PEF was measured before exercise and at five minute intervals for 30 minutes after exercise. Blood gas tensions were measured on capillary blood before, during, and 10 minutes after exercise. Treatment was not interrupted for this study. Mean PEF at rest was 87.6% (21.1%) predicted and showed no significant change after exercise. Mean PaO2 was 13.13 (1.37) kPa before exercise; it showed no significant change during exercise (13.93 (1.34) kPa) or 10 minutes after exercise (13.50 (2.15) kPa). Mean A-aDO2 also showed no change, being 1.82 (1.31) kPa before exercise, 1.79 (1.27) kPa during exercise, and 2.53 (0.93) kPa after exercise. It is concluded that moderate exercise carried out shortly after treatment for acute severe asthma is unlikely to result in worsening gas exchange during or after exercise if resting PEF, PaO2 and A-aDO2 have attained normal or near normal values.

Conference Abstract| December 01 1987 Changes in Resting Airflow and Exercise Ventilation in Asthma G E Packe; G E Packe 1Department of Respiratory Physiology, East Birmingham Hospital, Birmingham B9 5ST Search for other works by this author on: This Site PubMed Google Scholar W Freeman; W Freeman 1Department of Respiratory Physiology, East Birmingham Hospital, Birmingham B9 5ST Search for other works by this author on: This Site PubMed Google Scholar R M Cayton R M Cayton 1Department of Respiratory Physiology, East Birmingham Hospital, Birmingham B9 5ST Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1987) 73 (s17): 3P. https://doi.org/10.1042/cs073003Pa Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation G E Packe, W Freeman, R M Cayton; Changes in Resting Airflow and Exercise Ventilation in Asthma. Clin Sci (Lond) 1 December 1987; 73 (s17): 3P. doi: https://doi.org/10.1042/cs073003Pa Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1987 The Biochemical Society and the Medical Research Society1987 Article PDF first page preview Close Modal You do not currently have access to this content.

Virtually all primary non-Hodgkin's lymphomas of the lower respiratory tract affect the lung parenchyma and are associated with an abnormal chest radiograph.'We report a patient with non-Hodgkin's lymphoma of the mucosa of the major bronchi, who presented with reversible airflow obstruction.There was no other clinical or radiographic evidence of tumour and the disease responded rapidly and completely to radiotherapy. Case reportA 43 year old woman, who smoked 15 cigarettes a day, gave a six month history of increasing breathlessness on exertion, wheeze, and an unproductive cough.Physical examination revealed no abnormality.The chest radio- graph showed features consistent with emphysema.Spirometric measurements were: FEV, 2.1 1 (77% predicted), forced vital capacity (FVC) 4.5 1 (125%), and FEVI/FVC ratio 47%.The expiratory limb of a maximal l on May 31,

Virtually allprimary non-Hodgkin's lymphomas ofthe lower respiratory tract affect thelungparenchyma andare associated withanabnormal chest radiograph.' Wereport apatient withnon-Hodgkin's lymphoma ofthemucosa of themajorbronchi, whopresented withreversible airflow obstruction. Therewasnoother clinical orradiographic evidence oftumour andthedisease responded rapidly and completely toradiotherapy.

The dose-response relationships of a combination of the selective beta adrenergic agonist, fenoterol, and the synthetic anticholinergic drug, ipratropium bromide, were studied. In an open cross-over assessment, 20 patients with evidence of reversible airways obstruction inhaled 2, 4, 6 or 8 puffs from a metered dose inhaler, containing 100 micrograms fenoterol and 40 micrograms ipratropium bromide per puff, administered according to a randomization schedule, on four non-consecutive days. Before, and at intervals up to eight hours after inhalation FEV1, FVC, pulse and blood pressure were measured. Immediate and prolonged bronchodilatation followed each dose. The overall analysis of the FEV1, and FVC showed little difference between 2, 4 and 6 puffs. The highest dose, 8 puffs, was more effective, but associated with an increased incidence of side effects.