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Recent scientific developments have radically changed the way we look at the vast 'non-coding' part of our genome. It is now clear that this genomic 'dark matter' is transcribed into myriads of RNA species that act behind the scenes to veto, or boost, the production of proteins in our cells. As a consequence, non-coding RNAs (ncRNAs) represent an additional layer of regulation for fundamental biological processes such as organ development, tissue repair and immunity. It also follows that disturbances in ncRNA networks (among which microRNAs and long ncRNAs are the best studied) can give rise to a whole range of pathological conditions. Increasing preclinical and translational evidence places ncRNAs as key players in a wide spectrum of diseases affecting the lung. In this concise review, we will provide essential concepts of ncRNA science, with special emphasis on discoveries relevant to the pulmonary physician., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: In adults with asthma, ventilation heterogeneity, independent of inflammation, has been hypothesised to be associated with airway remodelling. Bronchial biopsy in preschool children with wheeze demonstrates early structural changes. Ventilation heterogeneity is sensitive to airway disease in other paediatric respiratory conditions such as cystic fibrosis, so may be sensitive to early airway disease in asthma. An observational study was performed in which it was hypothesised that ventilation heterogeneity (lung clearance index (LCI) and phase III slope indices (S(cond) and S(acin))) were more sensitive than conventional measurements (forced expiratory volume in 1 s (FEV(1)) and exhaled nitric oxide (Feno)) for detecting residual airways disease in children with well controlled asthma., Methods: In 31 children with asthma of mean age 10.6 years (range 5-15), FEV(1), LCI, S(cond) and S(acin) were measured at two separate visits, before and after blinded salbutamol or placebo, with Feno measured once. 29 healthy volunteers of mean age 11.2 years (range 5-16) completed measurements at one visit only., Results: Baseline mean (SD) LCI was significantly higher in children with asthma than in controls (6.69 (0.91) vs 6.24 (0.47), p = 0.02). There were no significant differences in FEV(1) or median Feno. Following salbutamol there was a small significant change in mean (SD) FEV(1) (from -1.26 (1.25) to -0.93 (0.23), p = 0.03) but not in LCI, S(cond) or S(acin). Importantly, LCI remained significantly higher after bronchodilator in children with asthma than in controls (6.64 (0.69), p = 0.01)., Conclusion: This study identifies the presence of residual ventilation heterogeneity in children with well controlled asthma and normal FEV(1). The role of LCI in measuring early airway disease in children with asthma requires further exploration, possibly as a surrogate of structural remodelling.

Background: The effect of respiratory medications on risk of asthma death in the UK was studied using the General Practice Research Database., Methods: A total of 96 258 individuals with a diagnosis of asthma were identified, 43 of whom had died as a result of their asthma. For each case 20 controls were selected. Relative risk (RR) estimates and 95% confidence intervals (CI) were computed for each respiratory drug category controlling for effects of age, sex, body mass index, smoking, frequency of visits to the GP, hospital admissions for asthma, and visits to a specialist., Results: The strongest associations were found for at least 13 prescriptions of short acting beta agonists during the previous year (RR=51.6, 95% CI 7.9 to 345) and 7-12 prescriptions of short acting beta agonists (RR=16.2, 95% CI 2.6 to 101). Short acting beta agonists and inhaled steroids tended to be prescribed most frequently to the same patients. In patients who received more than one prescription per month of short acting beta agonists during the previous year, regular use of inhaled steroids was associated with a 60% reduced risk of asthma death (RR=0.4, 95% CI 0.2 to 1.0)., Conclusions: Regular use of inhaled steroids is associated with a decreased risk of asthma death, and excessive use of short acting beta agonists is associated with a markedly increased risk of asthma death.

Background: Preterm infants often suffer from recurrent respiratory symptoms at follow up. Although these infants are responsive to treatment with bronchodilators some continue to wheeze or cough despite treatment. In a randomised double blind placebo controlled trial, the ability of inhaled steroids to reduce recurrent respiratory symptoms and the requirement for bronchodilator treatment in preterm infants less than two years of age has been assessed., Methods: Eighteen premature infants with mean gestational age 28 weeks and postnatal age 10.5 months were recruited. The study consisted of two six week treatment periods separated by a two week washout period. The infants received either 200 micrograms of beclomethasone dipropionate or placebo as one puff twice daily from an inhaler, through a spacer and a face mask. Parents kept a daily record of their infants' respiratory tract symptoms (wheeze and cough) and use of bronchodilators. Functional residual capacity (FRC) was measured at the beginning and end of each six week period., Results: The symptom score was reduced by 37% in the active compared with the placebo period. During the active period the infants had a mean of 28 bronchodilator free days, compared with 22 days in the placebo period. The FRC improved significantly in the active but not the placebo period., Conclusion: Regular dosage with beclomethasone by inhalation is a useful treatment for preterm infants with respiratory symptoms.

Respiratory function was studied in three groups of workers employed in processing coffee. The prevalence of almost all chronic respiratory symptoms was significantly higher in coffee processors than in control workers. In each group during the Monday work shift there was a significant mean acute decrease in the maximum expiratory flow rate at 50% vital capacity (VC), ranging from 4.0% to 8.7%, and at 25% VC, ranging from 6.0% to 18.5%. Acute reductions in FEV1.0 were considerably lower, ranging from 1.3% to 2.8%. On Thursdays the acute ventilatory function changes were somewhat lower than on Mondays. Acute decreases in flow rates at low lung volumes suggest that the bronchoconstrictor effect of the dust acts mostly on smaller airways. Administration of Intal (disodium cromoglycate) before the shift considerably diminished acute reductions in flow rates. A comparison of Monday pre-shift values of ventilatory capacity in coffee workers with those in controls indicates that exposure to dust in green or roasted coffee processing may lead to persistent loss of pulmonary function.

An open randomised comparison of a new intravenous cephalosporin, ceftazidime, with the established regimen of gentamicin and carbenicillin was carried out in patients with cystic fibrosis who had persisting pulmonary infection with Pseudomonas species and who developed acute exacerbations of respiratory symptoms. Fifty patients received ceftazidime and 32 gentamicin and carbenicillin. The ceftazidime and gentamicin were given every eight hours and the carbenicillin every six hours. The mean total daily doses were 151 mg/kg for ceftazidime, 6.3 mg/kg for gentamicin and 450 mg/kg for carbenicillin. The mean duration of treatment was 10 days in patients receiving gentamicin and carbenicillin and 12 days in those receiving ceftazidime. Of the patients with pseudomonas in the initial sputum specimen in whom sputum was cultured after treatment, six (26%) of 23 receiving gentamicin and carbenicillin and seven (18%) of 39 receiving ceftazidime had sputum free from pseudomonas at the end of treatment, but recolonisation occurred subsequently. In those receiving ceftazidime all 10 coexisting organisms were eliminated, whereas only four of seven coexisting organisms in patients receiving gentamicin and carbenicillin were eliminated. Overall clinical improvement occurred in 25 (78%) of 32 patients treated with gentamicin and carbenicillin and 48 (96%) of 50 patients treated with ceftazidime. Nineteen (59%) of the patients receiving gentamicin and carbenicillin but only 15 (30%) of those receiving ceftazidime required admission to hospital or intravenous antibiotics, or both, or died during the three months after treatment. Side effects in both groups were similar, mild, and infrequent. Thrombophlebitis occurred in four patients treated with gentamicin and carbenicillin but in no patients treated with ceftazidime.