Martin Jenkins

AstraZeneca, Tukholma, Stockholm, United Kingdom

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Publications (9)33.37 Total impact

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    ABSTRACT: ABSTRACT BACKGROUND: Paper-based diaries and self-report of symptom worsening in COPD studies may lead to under-detection of exacerbations. Epidemiologically, COPD exacerbations exhibit seasonal patterns peaking at year-end. We examined whether use of a BlackBerry-based daily symptom diary would detect 95% or more of exacerbations and enable characterization of seasonal differences between them. METHODS: Fifty participants with GOLD stage l to lV COPD began a community-based study in December 2007. Another 30 began in December 2008. Participants transmitted daily symptom diaries using a BlackBerry. Alerts were triggered when symptom changes, missed diary transmissions or medical care for a respiratory problem occurred. Participant encounters were initiated if COPD exacerbations were suspected. Participants reported returns to normal breathing using their BlackBerry. RESULTS: Participants transmitted 99.9% of 28,514 possible daily diaries. All 191 (2.5/participant-year) COPD exacerbations meeting Anthonisen criteria were detected. During 148/191 exacerbations (78%; 1.97/participant-year) patients were hospitalized and/or ordered prednisone, an antibiotic or both. Respiratory viruses were detected in 78/191 (41%) of exacerbations. Those coinciding with a respiratory viral infection averaged 12.0 days, those without averaged 8.9 days (P <.04), with no difference in Anthonisen score. Respiratory symptom scores before exacerbations and after normal breathing return showed no differences. Exacerbations were more frequent during the Christmas period than the rest of the year but not than the rest of winter alone. CONCLUSIONS: Smartphone-based collection of COPD symptom diaries enables near complete identification of exacerbations at inception. Exacerbation rates in the Christmas season do not reach levels that necessitate changes in disease management.
    Chest 03/2013; 144(2). DOI:10.1378/chest.12-2308 · 7.13 Impact Factor
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
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    ABSTRACT: Biomarkers play an increasingly important role in many aspects of pharmaceutical discovery and development, including personalized medicine and the assessment of safety data, with heavy reliance being placed on their delivery. Statisticians have a fundamental role to play in ensuring that biomarkers and the data they generate are used appropriately and to address relevant objectives such as the estimation of biological effects or the forecast of outcomes so that claims of predictivity or surrogacy are only made based upon sound scientific arguments. This includes ensuring that studies are designed to answer specific and pertinent questions, that the analyses performed account for all levels and sources of variability and that the conclusions drawn are robust in the presence of multiplicity and confounding factors, especially as many biomarkers are multidimensional or may be an indirect measure of the clinical outcome. In all of these areas, as in any area of drug development, statistical best practice incorporating both scientific rigor and a practical understanding of the situation should be followed. This article is intended as an introduction for statisticians embarking upon biomarker-based work and discusses these issues from a practising statistician's perspective with reference to examples.
    Pharmaceutical Statistics 11/2011; 10(6):494-507. DOI:10.1002/pst.532 · 1.10 Impact Factor
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    ABSTRACT: Asthma and chronic obstructive pulmonary disease (COPD) display features of overlap in airway physiology and airway inflammation. Whether inflammatory phenotypes in airway disease describe similar mediator expression is unknown. To explore the relationship of airway inflammation and cytokine and chemokine expression in asthma and COPD. Subjects with asthma and COPD (n = 54 and n = 49) were studied. Clinical characteristics and sputum were collected at entry into the study. A 2-step sputum processing method was performed for supernatant and cytospin preparation. Meso Scale Discovery and Luminex platforms were used to measure cytokines, chemokines and matrix metalloproteinase levels. Analytes sensitive to dithiothreitol (DTT) that had increased recovery in the 2-step sputum process were IL-1β, 4, 5, 10, 13, IFN-γ, TNFRI, GM-CSF, CCL2, 3, 4, 5, 13 and 17. There was a differential expression in IL-8, TNFRI and TNFRII between asthma and COPD [mean fold difference (95% CI): IL-8, 2.6 (1.3-5.4), p = 0.01; TNFRI, 2.1 (1.3-5.4), p = 0.03; TNFRII, 2.6 (1.2-5.6), p = 0.02]. In neutrophilic and eosinophilic airway inflammation, TNFα, TNFRI, TNFRII, IL-6, IL-8 and IL-5 could differentiate between these phenotypes. However, these phenotypes were unrelated to the diagnosis of asthma or COPD. Recovery of sputum mediators sensitive to DTT can be improved using the described sputum processing technique. Within airway inflammatory sub-phenotypes there is a differential pattern of mediator expression that is independent of disease. Whether these inflammatory phenotypes in asthma and COPD confer distinct pathogeneses, therapeutic responses and clinical phenotypes needs to be further evaluated.
    Respiration 09/2011; 83(1):36-44. DOI:10.1159/000330667 · 2.92 Impact Factor
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    ABSTRACT: Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology. Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation. Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated. Measurements and Main Results: A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed “pauciinflammatory.” Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1β, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83–0.95); serum CXCL10, 0.83 (95% CI, 0.70–0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78–0.93), respectively. The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1β, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.
    American Journal of Respiratory and Critical Care Medicine 06/2011; 184(6):662-71. DOI:10.1164/rccm.201104-0597OC · 11.99 Impact Factor
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    ABSTRACT: Background Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous in their aetiology and inflammatory response. We investigated the presence of biological phenotypes of COPD exacerbations and biomarker associations with pathogens and inflammation. Method Patients with COPD were observed for 1 year at stable and exacerbation visits. Spirometry, health quality assessments, blood and sputum (for differential cell counts) were collected at each visit. A large panel of biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biomarkers that differentiated exacerbations associated with bacteria, viruses or eosinophilic airway inflammation were investigated. Biological phenotypes were explored using cluster analysis. Result 145 patients (101 men, 44 women) entered the study. 182 exacerbations were captured from 86 patients. 55%, 26% and 28% met our definitions for bacteria, virus or sputum eosinophil associated exacerbations. Respectively each of the associated exacerbations were best identified by sputum IL-1β (area under receiver operator curve 0.89 (95% CI 0.83 to 0.95), serum CXCL10 (IP-10) 0.83 (0.70 to 0.96), and percentage peripheral blood eosinophils 0.85 (0.78 to 0.93). The odds ratio (95% CI) of an eosinophil or bacteria associated exacerbation was 2.7 (1.3 to 5.7) and 4.9 (2.4 to 9.9) if a sputum eosinophilia or bacterial pathogen was detected on ≥1 occasion at stable state. Four biological clusters were identified which validated the subgroups of exacerbations associated with bacteria, virus or sputum eosinophilia. Conclusion COPD exacerbation heterogeneity can be defined. Sputum IL-1β, serum CXCL10 (IP-10) and percentage peripheral blood eosinophils could be used to identify bacteria, virus or eosinophil associated exacerbations of COPD. Whether these biomarkers can be applied to direct therapy warrants further investigation.
    Thorax 11/2010; 65(Suppl 4):A3-A3. DOI:10.1136/thx.2010.150896.6 · 8.56 Impact Factor
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    ABSTRACT: Epidemics of hospitalization for chronic obstructive pulmonary disease (COPD) occur annually during the Christmas holidays, and COPD exacerbations commonly coincide with respiratory viral infections. To compare the incidence and determinants of COPD exacerbations occurring between the Christmas holiday period and the remainder of the winter season. Seventy-one subjects with COPD of mixed severity faxed daily symptom diaries to a computer monitoring system from December 1, 2006, to April 30, 2007. Possible exacerbations prompted a home visit for assessment, spirometry and specimen collection for virological testing. Study subjects submitted a total of 95.4% of possible daily symptom diary sheets by fax. Of 114 possible COPD exacerbations detected using the faxed diaries, 110 met the Anthonisen criteria for true exacerbations. A total of 47 exacerbations (mean 6.7/week) occurred during the Christmas holiday period, while 63 exacerbations (mean 4.3/week) occurred during the remainder of winter. Of the Christmas period exacerbations and of those in the balance of winter, 21 (44%) and 20 (32%), respectively, coincided with respiratory viral infections. The incidence of COPD exacerbations during the Christmas period was greater than during the rest of winter in 2006/2007 and peaked immediately before Christmas - in contrast to hospital presentation for COPD, which peaked during the Christmas week. No clear role of respiratory viral infections in the increased rate of exacerbations during the Christmas period was established in the present study. COPD patients were highly compliant with daily symptom reporting using faxed daily diaries, which permitted nearly complete detection of all exacerbations that occurred at incidence.
    Canadian respiratory journal: journal of the Canadian Thoracic Society 11/2010; 17(6):275-81. · 1.66 Impact Factor
  • American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans; 05/2010
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