HIPTox-Hazard Identification Platform to Assess the Health Impacts from Indoor and Outdoor Air Pollutant Exposures, through Mechanistic Toxicology: A Single-Centre Double-Blind Human Exposure Trial Protocol.

Over the past decade, our understanding of the impact of air pollution on short- and long-term population health has advanced considerably, focusing on adverse effects on cardiovascular and respiratory systems. There is, however, increasing evidence that air pollution exposures affect cognitive function, particularly in susceptible groups. Our study seeks to assess and hazard rank the cognitive effects of prevalent indoor and outdoor pollutants through a single-centre investigation on the cognitive functioning of healthy human volunteers aged 50 and above with a familial predisposition to dementia. Participants will all undertake five sequential controlled exposures. The sources of the air pollution exposures are wood smoke, diesel exhaust, cleaning products, and cooking emissions, with clean air serving as the control. Pre- and post-exposure spirometry, nasal lavage, blood sampling, and cognitive assessments will be performed. Repeated testing pre and post exposure to controlled levels of pollutants will allow for the identification of acute changes in functioning as well as the detection of peripheral markers of neuroinflammation and neuronal toxicity. This comprehensive approach enables the identification of the most hazardous components in indoor and outdoor air pollutants and further understanding of the pathways contributing to neurodegenerative diseases. The results of this project have the potential to facilitate greater refinement in policy, emphasizing health-relevant pollutants and providing details to aid mitigation against pollutant-associated health risks.

Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH): a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial.

BACKGROUND: Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease, with most patients reporting cough. Currently, there are no proven treatments. We examined the use of low dose controlled-release morphine compared with placebo as an antitussive therapy in individuals with idiopathic pulmonary fibrosis. METHODS: The PACIFY COUGH study is a phase 2, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial done in three specialist centres in the UK. Eligible patients aged 40-90 years had a diagnosis of idiopathic pulmonary fibrosis within 5 years, self-reported cough (lasting >8 weeks), and a cough visual analogue scale (VAS) score of 30 mm or higher. Patients were randomly assigned (1:1) to placebo twice daily or controlled-release morphine 5 mg orally twice daily for 14 days followed by crossover after a 7-day washout period. Patients were randomised sequentially to a sequence group defining the order in which morphine and placebo were to be given, according to a computer-generated schedule. Patients, investigators, study nurses, and pharmacy personnel were masked to treatment allocation. The primary endpoint was percentage change in objective awake cough frequency (coughs per h) from baseline as assessed by objective digital cough monitoring at day 14 of treatment in the intention-to-treat population, which included all randomised participants. Safety data were summarised for all patients who took at least one study drug and did not withdraw consent. This study was registered at ClinicalTrials.gov, NCT04429516, and has been completed. FINDINGS: Between Dec 17, 2020, and March 21, 2023, 47 participants were assessed for eligibility and 44 were enrolled and randomly allocated to treatment. Mean age was 71 (SD 7·4) years, and 31 (70%) of 44 participants were male and 13 (30%) were female. Lung function was moderately impaired; mean forced vital capacity (FVC) was 2·7 L (SD 0·76), mean predicted FVC was 82% (17·3), and mean predicted diffusion capacity of carbon monoxide was 48% (10·9). Of the 44 patients who were randomised, 43 completed morphine treatment and 41 completed placebo treatment. In the intention-to-treat analysis, morphine reduced objective awake cough frequency by 39·4% (95% CI -54·4 to -19·4; p=0·0005) compared with placebo. Mean daytime cough frequency reduced from 21·6 (SE 1·2) coughs per h at baseline to 12·8 (1·2) coughs per h with morphine, whereas cough rates did not change with placebo (21·5 [SE 1·2] coughs per h to 20·6 [1·2] coughs per h). Overall treatment adherence was 98% in the morphine group and 98% in the placebo group. Adverse events were observed in 17 (40%) of 43 participants in the morphine group and six (14%) of 42 patients in the placebo group. The main side-effects of morphine were nausea (six [14%] of 43 participants) and constipation (nine [21%] of 43). One serious adverse event (death) occurred in the placebo group. INTERPRETATION: In patients with cough related to idiopathic pulmonary fibrosis, low dose controlled-release morphine significantly reduced objective cough counts over 14 days compared with placebo. Morphine shows promise as an effective treatment to palliate cough in patients with idiopathic pulmonary fibrosis, and longer term studies should be the focus of future research. FUNDING: The Jon Moulton Charity Trust.

A double-blind randomised placebo-controlled trial investigating the effects of lesogaberan on the objective cough frequency and capsaicin-evoked coughs in patients with refractory chronic cough.

Objective: Baclofen is a centrally acting γ-aminobutyric acid type B (GABAB) receptor agonist which reduces gastro-oesophageal reflux and suppresses the cough reflex; however, central nervous system side-effects limit its use. Lesogaberan is a novel peripherally acting GABAB agonist, but its effects on refractory chronic cough are unknown. Design: We performed a single-centre, placebo-controlled, double-blind randomised crossover study in patients with chronic cough, refractory to the treatment of underlying conditions. Patients were randomised to treatment with lesogaberan 120 mg modified release twice daily or matched placebo for 2 weeks and then crossed over to the alternative therapy after a 2-week washout. The primary end-point was 24-h cough frequency measured with an acoustic monitoring system. In addition, cough responses to capsaicin were measured, and gastro-oesophageal reflux assessed by 24-h pH/impedance at screening. Results: 22 patients were randomised to receive lesogaberan/placebo or placebo/lesogaberan (female (73%); mean±sd age 63.7±7.2 years; median (interquartile range) cough duration 10.5 (5.8-17.0) years; mean (95% CI) 45 (29-67) reflux events in 24 h; two patients had abnormal oesophageal acid exposure times). Although lesogaberan reduced cough counts by 26% over placebo, this did not reach statistical significance (p=0.12). However, lesogaberan did significantly improve cough responses to capsaicin (p=0.04) and the number of cough bouts (p=0.04) compared with placebo. Lesogaberan was well tolerated in this study. Conclusions: Lesogaberan improved cough hypersensitivity and the number of bouts of coughing, but not coughs per hour. This implies a possible role for peripheral GABAB receptors in refractory chronic cough.

Effect of centrally and peripherally acting GABAB agonism on the healthy human cough reflex.

BACKGROUND: Currently there are no effective licensed anti-tussive therapies. Understanding how the neuronal mechanisms mediating the cough reflex in animal models translate to humans is important for the development of effective therapies. Pre-clinical studies suggest that the activation of GABAB receptors in both the peripheral and central nervous systems inhibit cough. OBJECTIVE: To compare the effect of central and peripherally acting GABAB agonists (lesogaberan and baclofen) on the cough reflex in healthy volunteers. METHODS: We performed a single center, double-blind, double-dummy, three-way crossover trial in healthy controls comparing single doses of lesogaberan (120 mg MR), with baclofen (40 mg) and placebos. Cough responses to inhaled capsaicin were assessed at screening and 2h post-dose on each study day. The primary endpoint was the maximum number of coughs evoked at any concentration of capsaicin (Emax) and the secondary endpoint was the concentration evoking 50% of the maximal response (ED50). RESULTS: Fifteen participants enrolled onto the study (median age 29 (IQR 25-44) years; 7 females, mean BMI 24.6(±3.0). Lesogaberan treatment produced a small, statistically significant increase in Emax compared with placebo [mean 13.4coughs (95%CI 10.1-17.9) vs. 11.8coughs (8.8-15.9), p = 0.04], but had no effect on ED50 [geometric mean 47.4 µM (95%CI 24.4-91.7) vs 37.6 µM (95%CI 19.2-73.5), p = 0.37]. In contrast, baclofen had no significant effect on Emax (11.1, 95%CI 8.1-15.4) (p = 0.23), but significantly increased ED50 compared with placebo (geometric mean 75.2 µM (95%CI 37.2-151.8), p = 0.002). CONCLUSION: This data suggests the anti-tussive actions of GABAB agonists, in healthy volunteers, occur in the central rather than the peripheral nervous system.

Triggers of breathlessness in inducible laryngeal obstruction and asthma.

BACKGROUND: Inducible laryngeal obstruction (ILO) is often misdiagnosed as, or may coexist with, asthma. Identifying differences in triggering factors may assist clinicians to differentiate between the two conditions and could give mechanistic insights. OBJECTIVE: To identify and compare patient-reported triggers in ILO and asthma. METHODS: This was a two-part study. Initially, we conducted a retrospective case note review of the triggers of ILO from endoscopically confirmed ILO patients to generate a Breathlessness Triggers Survey (BrTS). Triggers were categorized as scents, environmental factors, temperature, emotions, mechanical factors and daily activities. Secondly, ILO and/or asthma patients completed the BrTS prospectively, rating the likelihood of each item triggering their symptoms using a five-point Likert scale (strongly disagree to strongly agree). Chi-square testing was performed to compare responses by cohort. RESULTS: Data from 202 patients with ILO [73% female, mean (SD) age 53(16) years] were included in the case note review. For the prospective study, 38 patients with ILO only [63% females, age 57(16) years], 39 patients with asthma only [(56% female, age 53(13) years] and 12 patients with both ILO and asthma [83% female, mean age, 57 (14) years)] completed the BrTS. The triggers identified in the case note review were confirmed in the independent sample of patients with ILO and/or asthma and identified several difference in prevalence of the triggers between disease types. Mechanical factors (talking [P < .001], shouting [P = .007] and swallowing [P = .002]) were more common in the ILO cohort compared to patients with asthma. Environmental factors (pollen/flowers [P = .005] and damp air [P = .012]) were more common in asthma. There were no differences between groups in frequency of reporting scents as triggers (except for vinegar, more common in ILO, P = .019), temperature, emotions or daily activities. CONCLUSION: There were notable differences between patient-reported triggers of ILO and asthma, which may support clinician differential diagnosis.

ERS guidelines on the diagnosis and treatment of chronic cough in adults and children.

These guidelines incorporate the recent advances in chronic cough pathophysiology, diagnosis and treatment. The concept of cough hypersensitivity has allowed an umbrella term that explains the exquisite sensitivity of patients to external stimuli such a cold air, perfumes, smoke and bleach. Thus, adults with chronic cough now have a firm physical explanation for their symptoms based on vagal afferent hypersensitivity. Different treatable traits exist with cough variant asthma (CVA)/eosinophilic bronchitis responding to anti-inflammatory treatment and non-acid reflux being treated with promotility agents rather the anti-acid drugs. An alternative antitussive strategy is to reduce hypersensitivity by neuromodulation. Low-dose morphine is highly effective in a subset of patients with cough resistant to other treatments. Gabapentin and pregabalin are also advocated, but in clinical experience they are limited by adverse events. Perhaps the most promising future developments in pharmacotherapy are drugs which tackle neuronal hypersensitivity by blocking excitability of afferent nerves by inhibiting targets such as the ATP receptor (P2X3). Finally, cough suppression therapy when performed by competent practitioners can be highly effective. Children are not small adults and a pursuit of an underlying cause for cough is advocated. Thus, in toddlers, inhalation of a foreign body is common. Persistent bacterial bronchitis is a common and previously unrecognised cause of wet cough in children. Antibiotics (drug, dose and duration need to be determined) can be curative. A paediatric-specific algorithm should be used.

Management of Dyspnea and Anxiety in Chronic Obstructive Pulmonary Disease: A Critical Review.

BACKGROUND: Anxiety and dyspnea, 2 major symptoms in patients with chronic obstructive pulmonary disease (COPD), are associated with high morbidity and mortality. Thus, critically evaluating and synthesizing the existing literature employing pulmonary rehabilitation (PR) and other behavioral therapies in the treatment of anxiety and dyspnea in patients with COPD may help clinicians determine the most efficacious potential treatments. We aim to examine the efficacy of PR and behavioral therapy [eg, cognitive behavioral therapy (CBT) and counseling] and other adjunct modalities used in patients with COPD. METHODS: We extracted relevant studies searching the published literature using an electronic database CINAHL, Medline, PubMed, Science Direct, and the Web of Science was conducted (spanning January 1, 2006 to November 15, 2016). Studies were included if they conducted PR and behavioral therapy (CBT, self-management, yoga) to treat anxiety and/or dyspnea in patients with COPD with or without randomized controlled trial. RESULTS: The 47 studies selected included 4595 participants (PR = 3756 and behavioral therapy = 839), ranging in age from 58 to 75 years. The total number of participants receiving a treatment was 3928, and 667 participants served in control groups. In the majority of studies, PR and CBT are effective in the treatment of anxiety and dyspnea in the short term, but the long-term benefit is limited. In addition, self-management, yoga therapy, and CBT plus PR were beneficial. CONCLUSIONS: PR and CBT reduced both anxiety and dyspnea symptoms in patients with COPD in the short term. However, maintenance programs and the long-term benefits of PR and CBT remain inconclusive. Generally, the studies were relatively small and uncontrolled. Thus, prospective and randomized controlled trials with larger sample sizes are needed.

Assessment of Breathlessness in Lung Cancer: Psychometric Properties of the Dyspnea-12 Questionnaire.

CONTEXT: The Dyspnea-12 (D-12) Questionnaire is a well-validated instrument in respiratory illnesses for breathlessness assessment, but its psychometric properties have not been tested in lung cancer. OBJECTIVE: To demonstrate the psychometric properties of the D-12 in lung cancer patients. METHODS: Baseline data from a lung cancer feasibility trial were adopted for this analysis. D-12 and a series of patient-reported tools, including five Numeric Rating Scales (NRS), the Hospital Anxiety and Depression Scale (HADS), and the Lung Cancer Symptom Scale (LCSS), were used for the psychometric assessment. Spearman's correlation coefficients (rs) were used to estimate the convergent validity of the D-12 with the NRS, HADS, and LCSS. Exploratory factor analysis was performed to examine construct validity. Reliability was tested by Cronbach's alpha and item-to-total correlations. D-12 score difference between patients with or without anxiety, depression, and chronic obstructive pulmonary disease (COPD) was explored to identify its discriminate performance. RESULTS: One hundred and one lung cancer patients were included. There were significantly positive correlations between the D-12 and the HADS, LCSS, and NRS measuring breathlessness severity and its associated affective distress. Factor analysis clearly identified two components (physical and emotional) of the D-12. Cronbach's alpha for D-12 total, physical, and emotional subscales was 0.95, 0.92, and 0.94, respectively. Patients with anxiety or depression demonstrated significantly higher D-12 scores than those without it, and patients with COPD reported significantly more severe breathlessness than those without COPD. CONCLUSION: The D-12 is a valid and reliable self-reported questionnaire for use in breathlessness assessment in lung cancer patients.

Management of the respiratory distress symptom cluster in lung cancer: a randomised controlled feasibility trial.

BACKGROUND: Breathlessness, cough and fatigue are distressing symptoms for patients with lung cancer. There is evidence that these three symptoms form a discreet symptom cluster. This study aimed to feasibly test a new non-pharmacological intervention for the management of the Respiratory Distress Symptom Cluster (breathlessness-cough-fatigue) in lung cancer. METHOD: This was a multi-centre, randomised controlled non-blinded parallel group feasibility trial. Eligible patients (patients with primary lung cancer and 'bothered' by at least two of the three cluster symptoms) received usual care plus a multicomponent intervention delivered over two intervention training sessions and a follow-up telephone call or usual care only. Follow-up was for 12 weeks, and end-points included six numerical rating scales for breathlessness severity, Dyspnoea-12, Manchester Cough in Lung Cancer scale, FACIT-Fatigue scale, Hospital Anxiety and Depression scale, Lung Cancer Symptom Scale and the EQ-5D-3L, collected at baseline, week 4 and week 12. RESULTS: One hundred seven patients were randomised over 8 months; however, six were removed from further analysis due to protocol violations (intervention group n = 50 and control group n = 51). Of the ineligible patients (n = 608), 29 % reported either not experiencing two or more symptoms or not being 'bothered' by at least two symptoms. There was 29 % drop-out by week 4, and by week 12, a further two patients in the control group were lost to follow-up. A sample size calculation indicated that 122 patients per arm would be needed to detect a clinically important difference in the main outcome for breathlessness, cough and fatigue. CONCLUSIONS: The study has provided evidence of the feasibility and acceptability of a new intervention in the lung cancer population and warrants a fully powered trial before we reach any conclusions. The follow-on trial will test the hypothesis that the intervention improves symptom cluster of breathlessness, cough and fatigue better than usual care alone. Full economic evaluation will be conducted in the main trial.

[Not Available]. / Une version franco-canadienne de la Physiotherapy Evidence Database (PEDro) Scale : L'Échelle PEDro.

PURPOSE: To prepare a Canadian French translation of the PEDro Scale under the proposed name l'Échelle PEDro, and to examine the validity of its content. METHODS: A modified approach of Vallerand's cross-cultural validation methodology was used, beginning with a parallel back-translation of the PEDro scale by both professional translators and clinical researchers. These versions were reviewed by an initial panel of experts (P1), who then created the first experimental version of l'Échelle PEDro. This version was evaluated by a second panel of experts (P2). Finally, 32 clinical researchers evaluated the second experimental version of l'Échelle PEDro, using a 5-point clarity scale, and suggested final modifications. RESULTS: The various items on the final version of l'Échelle PEDro show a high degree of clarity (from 4.0 to 4.7 on the 5-point scale). CONCLUSION: The four rigorous steps of the translation process have produced a valid Canadian French version of the PEDro scale.

17q12-21 variants are associated with asthma and interact with active smoking in an adult population from the United Kingdom.

BACKGROUND: Although an association between 17q12-21 and asthma has been replicated across different populations, some inconsistencies have been found between different studies. OBJECTIVE: We investigated the association between genetic variation in this region with asthma, lung function, airway inflammation, hyperresponsiveness (AHR), and atopy in a case-control study of United Kingdom adults. The interaction between genotype and smoking was also evaluated. METHODS: Study subjects (n = 983) were carefully phenotyped using questionnaires, measurement of lung function, AHR (methacholine challenge), exhaled nitric oxide (eNO), and assessment of atopic status. Blood/saliva/buccal swabs were collected, and 47 single nucleotide polymorphisms (SNPs) in 17q12-21 were genotyped using MALDI-TOF (Matrix-assisted LASER desorption/ionisation-time of flight) mass spectrometry. We conducted a comprehensive investigation of 28 common SNPs within 6 genes of interest (IKZF3, ZPBP2, ORMDL3, GSDMA, GSDMB, TOP2A). RESULTS: Sixteen SNPs were significantly associated with asthma after multiple testing correction (P ≤ .01), of which 5 (rs2290400, rs8079416, rs3894194, rs7212938, and rs3859192) were strongly associated (FDR P ≤ .0002), and one was novel (IKZF3-rs1453559). For 3 of these SNPs, we found significant interaction with smoking and asthma (rs12936231, rs2290400, and rs8079416). Smoking modified the associations between 8 SNPs and lung function (rs9911688, rs9900538, rs1054609, rs8076131, rs3902025, rs3859192, rs11540720, and rs11650680). We observed significant interaction between 5 SNPs and smoking on AHR, and 3 interacted with smoking in relation to asthma with AHR (rs4795404, rs4795408, rs3859192). CONCLUSION: We found 1 novel association and replicated several previously reported associations between 17q12-21 polymorphisms and asthma. We demonstrated significant interactions between active smoking and polymorphisms in 17q12-21 with asthma, lung function, and AHR in adults. Our data confirm that 17q12-21 is an important asthma susceptibility locus.

Understanding cough and its management in lung cancer.

PURPOSE OF REVIEW: This article summarizes the current understanding of cough in lung cancer, strategies for its management and highlights areas where further research is warranted.Cough is common, severe and distressing for many lung cancer patients. Currently few effective cough interventions exist for lung cancer patients. This review proposes some of the mechanisms that may underlie cough in lung cancer and presents the existing data on antitussive therapy in cancer patients. A greater focus on the cough mechanisms may enable effective antitussives to be developed in the future for lung cancer patients. A brief overview of the validated cough assessment tools is provided. The use of such tools will enable robust clinical endpoints to be determined for future cough intervention studies. A 'cough treatment pyramid' is presented to provide a pragmatic approach to the management of cough in lung cancer patients. RECENT FINDINGS: Despite the small number of publications on cough in lung cancer, some recent research has characterized cough for the first time in lung cancer patients. Its impact on quality of life domains such as psychological, social and physical is significant. The lung cancer symptom cluster of cough, breathlessness and fatigue has also been described. A recently developed cough severity assessment tool has provided researchers with a short well validated seven-item questionnaire to determine this important cough characteristic. In addition, a Cochrane Database Systematic Review on Interventions for Cough in Cancer has also been published. These studies are all described in the present review. Understanding the impact of a symptom such as cough, the assessment of cough and its potential underlying mechanisms is crucial if we are to manage this symptom effectively. SUMMARY: Current cough management in lung cancer patients is lagging behind the management of other cancer symptoms. There is now an increasing need to diagnose and treat cough more effectively, as lung cancer patients are living longer with chronic symptoms such as cough.

Quantification of atopy, lung function and airway hypersensitivity in adults.

BACKGROUND: Studies in children have shown that concentration of specific serum IgE (sIgE) and size of skin tests to inhalant allergens better predict wheezing and reduced lung function than the information on presence or absence of atopy. However, very few studies in adults have investigated the relationship of quantitative atopy with lung function and airway hyperresponsiveness (AHR). OBJECTIVE: To determine the association between lung function and AHR and quantitative atopy in a large sample of adults from the UK. METHODS: FEV1 and FVC (% predicted) were measured using spirometry and airway responsiveness by methacholine challenge (5-breath dosimeter protocol) in 983 subjects (random sample of 800 parents of children enrolled in a population-based birth cohort enriched with 183 patients with physician-diagnosed asthma). Atopic status was assessed by skin prick tests (SPT) and measurement of sIgE (common inhalant allergens). We also measured indoor allergen exposure in subjects' homes. RESULTS: Spirometry was completed by 792 subjects and 626 underwent methacholine challenge, with 100 (16.0%) having AHR (dose-response slope>25). Using sIgE as a continuous variable in a multiple linear regression analysis, we found that increasing levels of sIgE to mite, cat and dog were significantly associated with lower FEV1 (mite p = 0.001, cat p = 0.0001, dog p = 2.95 × 10-8). Similar findings were observed when using the size of wheal on skin testing as a continuous variable, with significantly poorer lung function with increasing skin test size (mite p = 8.23 × 10-8, cat p = 3.93 × 10-10, dog p = 3.03 × 10-15, grass p = 2.95 × 10-9). The association between quantitative atopy with lung function and AHR remained unchanged when we repeated the analyses amongst subjects defined as sensitised using standard definitions (sIgE>0.35 kUa/l, SPT-3 mm>negative control). CONCLUSIONS: In the studied population, lung function decreased and AHR increased with increasing sIgE levels or SPT wheal diameter to inhalant allergens, suggesting that atopy may not be a dichotomous outcome influencing lung function and AHR.

New insights in cough.

Chronic cough is common, blights patients' lives and is hard to treat. Chronic cough patients demonstrate high objective cough rates and as a group have increased cough reflex sensitivity. However, conventional cough challenge techniques show substantial overlap with normal subjects. This suggests that other important mechanisms have yet to be determined. For the last two decades, chronic cough has been considered to be caused by gastro-oesophageal reflux, post-nasal drip or asthma. However, many patients with these conditions do not have cough, and in those with cough, the response to specific treatments is unpredictable at best. In addition, many chronic cough patients do not have an identifiable cause. This raises questions about the concept of a triad of treatable causes for chronic cough. Our current understanding of the neurophysiology of the cough reflex is largely derived from animal work with limited data in humans. By analogy with chronic pain syndromes, both peripheral and central sensitization may be important mechanisms in chronic cough, and are under active investigation. We need to understand the mechanisms underlying sensitization, how they interact with cough triggers and their relationship with the sensations that drive the urge to cough, and the subsequent motor cough response in chronic cough. Only then will we develop effective interventions.

Interventions for cough in cancer.

BACKGROUND: Cough is a common symptom in patients with malignancies, especially in patients with lung cancer. Cough is not well controlled in clinical practice and clinicians have few management options to treat it. OBJECTIVES: The primary objective of this review was to determine the effectiveness of interventions, both pharmacological and non-pharmacological, (other than chemotherapy and external beam radiotherapy) in the management of cough in malignant disease (especially in lung cancer). SEARCH STRATEGY: Databases searched included: The Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effectiveness (DARE) (The Cochrane Library issue 4, 2009); MEDLINE (1966 to May 2010); EMBASE (1980 to May 2010); CINAHL (1980 to May 2010); PSYCHINFO (1980 to May 2010); AMED (1985 to May 2010); SIGLE (1980 to May 2010); British Nursing Index (1985 to May 2010); CancerLit (1975 to May 2010). We searched for cough suppressants, antitussives and other drugs with antitussive activity as well as non-pharmacological interventions (see Appendices 1-4 for search terms). SELECTION CRITERIA: We selected randomised controlled trials (RCTs) and clinical trials (quasi-experimental trials, and trials where there is a comparison group but no mention of randomisation) in participants with primary or metastatic lung cancer or other cancers. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed titles and abstracts of all studies, and extracted data from all selected studies before reaching consensus. A third review author arbitrated with any disagreement. Meta-analysis was not attempted due to the heterogeneity of studies. MAIN RESULTS: Seventeen studies met inclusion criteria and examined either brachytherapy, laser or photodynamic therapy (eight studies) or a variety of pharmacological therapies (nine studies). Overall, there was absence of credible evidence and the majority of studies were of low methodological quality and high risk of bias. Brachytherapy seemed to improve cough in a variety of doses in selected participants, suggesting that possibly the lowest effective dose should be used to minimise side effects. Photodynamic therapy was examined in one study, and while improvements in cough were observed, its role over other therapies for cough is unclear. Some indication of effect was observed with morphine, codeine, dihydrocodeine, levodropropizine, sodium cromoglycate and butamirate citrate linctus (cough syrup), although all studies had significant risk of bias. AUTHORS' CONCLUSIONS: No practice recommendations could be drawn from this review. There is an urgent need to increase the number and quality of studies evaluating the effects of interventions in the management of cough in cancer.

COPD phenotype description using principal components analysis.

BACKGROUND: Airway inflammation in COPD can be measured using biomarkers such as induced sputum and Fe(NO). This study set out to explore the heterogeneity of COPD using biomarkers of airway and systemic inflammation and pulmonary function by principal components analysis (PCA). SUBJECTS AND METHODS: In 127 COPD patients (mean FEV1 61%), pulmonary function, Fe(NO), plasma CRP and TNF-alpha, sputum differential cell counts and sputum IL8 (pg/ml) were measured. Principal components analysis as well as multivariate analysis was performed. RESULTS: PCA identified four main components (% variance): (1) sputum neutrophil cell count and supernatant IL8 and plasma TNF-alpha (20.2%), (2) Sputum eosinophils % and Fe(NO) (18.2%), (3) Bronchodilator reversibility, FEV1 and IC (15.1%) and (4) CRP (11.4%). These results were confirmed by linear regression multivariate analyses which showed strong associations between the variables within components 1 and 2. CONCLUSION: COPD is a multi dimensional disease. Unrelated components of disease were identified, including neutrophilic airway inflammation which was associated with systemic inflammation, and sputum eosinophils which were related to increased Fe(NO). We confirm dissociation between airway inflammation and lung function in this cohort of patients.