Graham Devereux

Definition, epidemiology, and risk factors

In 2004, the UK National Institute for Clinical Excellence defined chronic obstructive pulmonary disease (COPD) as “characterised by airflow obstruction. The airflow obstruction is usually progressive, not fully reversible and does not change markedly over several months. The disease is predominantly caused by smoking.” COPD is the preferred umbrella term for the airflow obstruction associated with the diseases of chronic bronchitis and emphysema. These are closely related to, but not synonymous with, COPD.nnnnView this table:nnDefinitions of conditions associated with airflow obstructionnnnnAlthough asthma is associated with airflow obstruction, it is usually considered as a separate clinical entity. Some patients with chronic asthma also develop airflow obstruction that is relatively fixed (a consequence of airway remodelling) and often indistinguishable from COPD. Because of the high prevalence of asthma and COPD, these conditions coexist in many patients, creating diagnostic uncertainty. Other conditions also associated with poorly reversible airflow obstruction include cystic fibrosis, bronchiectasis, and obliterative bronchiolitis. Although these conditions need to be considered in the differential diagnosis of obstructive airways disease, they are not conventionally covered by the definition of COPD.nn ![][1] nnPrevalence of diagnosed COPD in UK men and women during 1990-7nn### PrevalencennEstimating and comparing the prevalence of COPD in different countries is complicated by differences in its precise definition and in the level of underdiagnosis. For example, in the United Kingdom mild COPD is defined as the ratio of forced expiratory volume in 1 second (FEV1) to the forced vital capacity (FVC) being < 0.7 and the FEV1 being 50-80% of the expected value. Other guidelines suggest slightly different spirometric values (see third article in this series).nn ![][2] nnPrevalence of diagnosed COPD in UK men and women by age, during 1990-7nnA national UK study reported an abnormally low FEV1 in 10% of men and 11% of women aged 16-65 …nn [1]: /embed/graphic-2.gifn [2]: /embed/graphic-3.gif

A case–control study of vitamin D status and asthma in adults

1. Mari A, Iacovacci P, Afferni C, Barletta B, Tinghino R, Di Felice G et al. Specyfic IgE to crossreactive carbohydrate determinants strongly affect the in vitro diagnosis of allergic diseases. J Allergy Clin Immunol 1999;103:1005–1011. 2. van der Veen MJ, van Ree R, Aalberse RC, Akkerdaas J, Koppelman SJ, Jansen HM et al. Poor biologic activity of cross-reactive IgE directed to carbohydrate determinants of glycoproteins. J Allergy Clin Immunol 1997;100:327–334. 3. Mari A. IgE to crossreactive carbohydrate determinants: analysis of the distribution and appraisal of the in vivo and in vitro reactivity. Int Arch Allergy Immunol 2002; 129:286–295. 4. Mari A, Ooievaar-de Heer P, Scala E, Giani M, Pirrotta L, Zuidmeer L et al. Evaluation by double-blind placebo-controlled oral challenge of the clinical relevance of IgE antibodies against plant glycans. Allergy 2008; 63:891–896. 5. Malandain H. IgE-reactive carbohydrate epitopes-classification, cross-reactivity, and clinical impact (2nd part). Eur Ann Allergy Clin Immunol 2005;37:247–256. 6. van Ree R, Aalberse RC. Pollen – vegetable food cross-reactivity: serological and clinical relevance of cross-reactive IgE. J Clin Immunoassay 1993;16:124–130. 7. Raulf-Heimsoth M, Rihs HP, Rozynek P, Cremer R, Gaspar A, Pires G et al. Quantitative analysis of immunoglobulin E reactivity profiles in patients allergic or sensitized to natural rubber latex (Hevea brasiliensis). Clin Exp Allergy 2007;37: 1657–1667. 8. Altmann F. The role of protein glycosylation in allergy. Int Arch Allergy Immunol 2007;142:99–115.

Recent developments in asthma management

Asthma is a common chronic heterogeneous condition with several characteristic features (%fig 1). It can present in early childhood as well as in adulthood, and it varies markedly in severity, clinical course, subsequent disability, and response to treatment. In common with other atopic disorders such as allergic rhinitis, atopic dermatitis, and food allergy, the prevalence of asthma has risen over the past few decades in both developed and developing countries.1 The increasing burden of asthma in primary and secondary care has led to extensive research into its genetics, pathophysiology, and treatment. In this review, we highlight some of the recent developments in the clinical management of asthma and identify key areas in which further research is needed.nnnnFig 1 nThe key components of asthmannnnWe did a comprehensive literature search using Medline, Clinical Evidence, the Cochrane Library, and Embase. We used the following keywords in the search: acute asthma, chronic asthma, leucotriene receptor antagonist, long acting β2 agonist, inhaled corticosteroid, action plans, allergen, diet, magnesium, vitamin, Buteyko, anti-immunoglobulin E, and interleukin. We selected and extracted recent articles from 2000 onwards that we felt to be of relevance or interest to practising clinicians, as well as choosing topics that we were aware of being potentially important. All the authors are respiratory physicians with an interest in airways disease.nn### Non-pharmacological managementnn#### Allergen avoidancennAtopy and asthma are separate conditions with differing genetic and epidemiological associations. Although atopic sensitisation increases the likelihood of asthma, this is not an absolute association. Allergen avoidance is commonly recommended in patients with asthma, especially those who show type 1 hypersensitivity to common aeroallergens.1 2 However, a surprising lack of evidence based data exists to substantiate the effectiveness of this approach. Several major studies have specifically evaluated allergen avoidance and its impact on asthma control. In a double blind randomised placebo …

Comorbidity in Lung Cancer: Important but Neglected. A Review of the Current Literature

INTRODUCTIONnTreatment and survival rates for patients with lung cancer in Scotland appear lower than in many other European countries. Five-year survival is quoted at 6% to 7% compared with 8% to 15% in other European countries and America. There also appear to be variations in treatment rates within Scotland. Although this variation in treatment and survival is popularly interpreted as evidence of variation in facilities, access to care, and clinical practice, it is possible that the increased comorbidity and poor performance status of the Scottish population may contribute to the observed disparities in treatment and outcomes, although this has never been proven. The demonstration that comorbidity influences treatment and survival rates will have important implications for the targeting of health services resources, screening, interpretation of cancer statistics, and the assessment and management of patients with lung cancer.nnnMETHODSnIn this article we have reviewed the tools currently available for assessing comorbidity and in addition have identified published works which study the effect of comorbidity in lung cancer.nnnCONCLUSIONnThere is no currently validated measurement tool applicable specifically to lung cancer and thus there remains a significant need for further work in this important area. STATEMENT OF SEARCH STRATEGIES USED AND SOURCES OF INFORMATION: Literature searches were undertaken via PubMed and Google Scholar using various arrays of the following keywords: cancer, comorbidity, lung lancer, performance status, survival, and tools. The search was limited to articles published in peer-review journals with English as the language.

Variation in Comorbidity and Clinical Management in Patients Newly Diagnosed with Lung Cancer in Four Scottish Centers

Background: Treatment and survival rates within Scotland for patients with lung cancer seem lower than in many other European countries. No study of lung cancer has attempted to specifically investigate the association between variation in investigation, comorbidity, and treatment and outcome between different centers. Methods: Patient demographics, World Health Organization/Eastern Cooperative Oncology Group performance status, and primary treatment modality were recorded. In addition to recording the comorbidities present in each patient, the severity of each comorbidity was graded on a 4-point scale (0–3) using validated severity scales. Data were collected as the patient was investigated and entered in an anonymized format into a database designed for the study. Results: Prospectively collected data from 882 patients diagnosed with lung cancer in four Scottish centers. A number of statistically significant differences were identified between centers. These included investigation, treatment between centers (i.e., surgical rates), age, tumor histology, smoking history, socioeconomic profile, ventilatory function, and performance status. Predictors of declining performance status included increasing severity of a number of comorbidities, age, lower socioeconomic status, and specific centers. Conclusions: This study has identified many significant intercenter differences within Scotland. We believe this to be the first study to identify nontumor factors independent of performance status that together limit the ability to deliver radical, possibly curative, therapy to our lung cancer population. It is only by identifying such factors that we can hope to improve on the relatively poor outlook for the majority of Scottish patients with lung cancer.

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial

BackgroundChronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that ‘low dose’ theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of ‘low dose’ theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD.Method/DesignTWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either ‘low dose’ theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1–5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period.DiscussionThe demonstration that ‘low dose’ theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally.Trial registrationCurrent Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014.

A comparison between clinical decisions made about lung cancer patients and those inherent in the corresponding Scottish Intercollegiate Guidelines Network (SIGN) guideline.

Treatment and survival for patients with lung cancer vary between and within countries. We have undertaken a multifaceted study of a clinical dataset of 635 patients, to see if clinician treatment decisions were being made consistently and in accordance with the appropriate Scottish Intercollegiate Guidelines Network (SIGN) document. Subsequently, we created a dataset of 117 patients who should have undergone surgery according to the SIGN guideline. As analyses of this dataset did not provide clear distinctions between the main treatment groups, a clinician reviewed the case notes and dataset, checking for inconsistencies. The revised dataset was processed by a decision tree algorithm which suggests clinically plausible decisions. Further, statistical analyses compared the 54 patients offered surgery with the 52 who were not. These analyses suggest that there are significant differences: the most discriminating feature is significant co-morbidity (p < 0.001). The article concludes with suggestions for how future guidelines might be enhanced.

Aspergillus-induced superoxide production by cystic fibrosis phagocytes is associated with disease severity

Aspergillus fumigatus infects up to 50% of cystic fibrosis (CF) patients and may play a role in progressive lung disease. As cystic fibrosis transmembrane conductance regulator is expressed in cells of the innate immune system, we hypothesised that impaired antifungal immune responses play a role in CF-related Aspergillus lung disease. Peripheral blood mononuclear cells, polymorphonuclear cells (PMN) and monocytes were isolated from blood samples taken from CF patients and healthy volunteers. Live-cell imaging and colorimetric assays were used to assess antifungal activity in vitro. Production of reactive oxygen species (ROS) was measured using luminol-induced chemiluminescence and was related to clinical metrics as collected by case report forms. CF phagocytes are as effective as those from healthy controls with regards to phagocytosis, killing and restricting germination of A. fumigatus conidia. ROS production by CF phagocytes was up to four-fold greater than healthy controls (p<0.05). This effect could not be replicated in healthy phagocytes by priming with lipopolysaccharide or serum from CF donors. Increased production of ROS against A. fumigatus by CF PMN was associated with an increased number of clinical exacerbations in the previous year (p=0.007) and reduced lung function (by forced expiratory volume in 1u2005s) (p=0.014). CF phagocytes mount an intrinsic exaggerated release of ROS upon A. fumigatus stimulation which is associated with clinical disease severity. Excessive superoxide production by CF phagocytes against A. fumigatus is associated with clinical disease severity http://ow.ly/Elwy30i8mLe