Protocol 012 Investigators (2020). Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. The Lancet Respiratory Medicine.

Background Ongoing climate change might, through rising temperatures, alter allergenic pollen biology across the northern hemisphere. We aimed to analyse trends in pollen seasonality and pollen load and to establish whether there are specific climate-related links to any observed changes.Methods For this retrospective data analysis, we did an extensive search for global datasets with 20 years or more of airborne pollen data that consistently recorded pollen season indices (eg, duration and intensity). 17 locations across three continents with long-term (approximately 26 years on average) quantitative records of seasonal concentrations of multiple pollen (aeroallergen) taxa met the selection criteria. These datasets were analysed in the context of recent annual changes in maximum temperature (T max ) and minimum temperature (T min ) associated with anthropogenic climate change. Seasonal regressions (slopes) of variation in pollen load and pollen season duration over time were compared to T max , cumulative degree day T max , T min , cumulative degree day T min , and frost-free days among all 17 locations to ascertain significant correlations.Findings 12 (71%) of the 17 locations showed significant increases in seasonal cumulative pollen or annual pollen load. Similarly, 11 (65%) of the 17 locations showed a significant increase in pollen season duration over time, increasing, on average, 0•9 days per year. Across the northern hemisphere locations analysed, annual cumulative increases in T max over time were significantly associated with percentage increases in seasonal pollen load (r=0•52, p=0•034) as were annual cumulative increases in T min (r=0•61, p=0•010). Similar results were observed for pollen season duration, but only for cumulative degree days (higher than the freezing point [0°C or 32°F]) for T max (r=0•53, p=0•030) and T min (r=0•48, p=0•05). Additionally, temporal increases in frost-free days per year were significantly correlated with increases in both pollen load (r=0•62, p=0•008) and pollen season duration (r=0•68, p=0•003) when averaged for all 17 locations.Interpretation Our findings reveal that the ongoing increase in temperature extremes (T min and T max ) might already be contributing to extended seasonal duration and increased pollen load for multiple aeroallergenic pollen taxa in diverse locations across the northern hemisphere. This study, done across multiple continents, highlights an important link between ongoing global warming and public health-one that could be exacerbated as temperatures continue to increase.

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The majority of asthma exacerbations are caused by respiratory infections, with rhinovirus (RV) being the most common virus. Recent evidence has suggested that decreased generation of IFN-gamma is associated with more severe colds and delayed elimination of virus. Whether the generation of IFN-gamma also has any relationship to general features of asthma severity has yet to be determined. To evaluate this hypothesis, peripheral blood mononuclear cells from 19 subjects with atopy and asthma were incubated with RV16 for 6 days to determine IFN-gamma and interleukin (IL)-5 production; these responses were then compared with measurements of airflow obstruction and airway responsiveness. RV16-induced IFN-gamma production correlated significantly with the methacholine PD (r = 0.50, p = 0.03), and the ratio of RV16-induced IFN-gamma:IL-5 correlated with % predicted FEV1 (r = 0.53, p = 0.02). In contrast, there were no significant associations between measures of asthma severity and RV-induced IL-5. These findings suggest that a cytokine imbalance with a deficient Th1 response to RV, but not a Th2 response, is associated with measures of asthma severity and support the concept that impaired antiviral responses may be associated with asthma severity.

The aim of this study was to compare the efficacy and safety of salmeterol vs theophylline in asthma management using meta-analysis of clinical trials. Nine clinical studies, containing a total of 1330 patients, met meta-analysis inclusion criteria: randomized, controlled study, minimum 2-week treatment duration with either salmeterol or theophylline. The main outcome measurements were morning and evening peak expiratory flow rate (PEFR), morning and evening symptom scores, use of salbutamol as rescue medication, and withdrawal from treatment for any cause. During the second week of treatment, salmeterol patients had a 10 l min-1 greater increase in mean morning PEFR from baseline than theophylline patients (P < 0.001). Similarly, in the second week, the increase in mean evening PEFR from baseline observed with salmeterol was significantly greater (P < 0.01) than that observed with theophylline. Salmeterol also produced a significantly greater increase in mean morning and evening PEFR than theophylline at weeks 3 and 4. Patients receiving salmeterol were free from daytime symptoms for a mean of 51% of days in the second week compared to 39% for theophylline patients (P < 0.001). Salmeterol patients experienced a mean of 63% symptom-free nights compared to 52% for theophylline patients (P < 0.001). Rescue medication with salbutamol was not required on 49% of days for salmeterol patients and 34% of days for theophylline patients. All results were maintained in the third and fourth weeks of treatment. Withdrawal and incidence of adverse events leading to withdrawal were significantly less frequent in patients receiving salmeterol (P < 0.001). Thus, this meta-analysis suggests that salmeterol has a superior safety and efficacy profile to theophylline in the management of symptoms of chronic asthma.

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Infections have a variety of influences in the asthmatic patient. Respiratory syncytial virus (RSV) is the most common cause of wheezing illnesses in children under the age of 2 years and may be a risk factor for the inception of asthma in the first decade of life. Once asthma has become recognized clinically, rhinovirus is the leading cause of acute asthma exacerbations in adults and older children. Certain respiratory infections may induce chronic lower airway inflammation that may contribute to disease progression or severity in asthma. Paradoxically, some infections may even protect against the development of asthma. This article reviews the evidence for these associations and the mechanisms proposed to explain these various outcomes.

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