Prevalence and clinical features of most frequent phenotypes in the Italian COPD population: the CLIMA Study

Roberto W. Dal Negro; Mauro Carone; Giuseppina Cuttitta; Luca Gallelli; Massimo Pistolesi; Salvatore Privitera; Piero Ceriana; Pietro Pirina; Bruno Balbi; Carlo Vancheri; Franca M. Gallo; Alfredo Chetta; Paola Turco; on behalf of the  CLIMA Study Group*

doi:10.4081/mrm.2021.790

Prevalence and clinical features of most frequent phenotypes in the Italian COPD population: the CLIMA Study

Authors

Roberto W. Dal Negro National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology - CESFAR, Verona
Mauro Carone ICS Maugeri IRCCS, Cassano delle Murge (BA) https://orcid.org/0000-0002-5478-8521
Giuseppina Cuttitta Institute of Biomedicine and Molecular Immunology, National Research Council, Palermo
Luca Gallelli Pharmacology Operative Unit, University Hospital Authority “Mater Domini”, Catanzaro
Massimo Pistolesi Pneumologia e Fisiopatologia Toraco-Polmonare, Azienda Ospedaliera Universitaria Careggi, Firenze
Salvatore Privitera C.P.M., Giarre (CT)
Piero Ceriana Occupational Health and Rehabilitation Clinic, ICS Maugeri IRCCS, Pavia https://orcid.org/0000-0002-4186-4257
Pietro Pirina Pneumology Operative Unit, University Hospital Authority, Sassari
Bruno Balbi Pneumology Rehabilitation Unit, ICS Maugeri IRCCS, Veruno (NO)
Carlo Vancheri Pneumology Rehabilitation Unit, University Hospital Authority, Policlinico Vittorio Emanuele, Catania
Franca M. Gallo Departmental Structure for Territorial Pneumology, Local Health Authority, Matera
Alfredo Chetta Pneumology Clinic, University Hospital Authority, Hospital “G. Rasori”, Parma https://orcid.org/0000-0002-0416-5334
Paola Turco Research and Clinical Governance, Verona
on behalf of the CLIMA Study Group*

DOI: https://doi.org/10.4081/mrm.2021.790

Keywords:

COPD, COPD phenotypes, clinical pictures, chronic bronchitis, emphysema, bronchial asthma, airway disease

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a complex, progressive respiratory condition characterized by heterogeneous clinical presentations (phenotypes). The aim of this study was to assess the prevalence of the main COPD phenotypes and match each phenotype to the most fitting clinical and lung function profile.
Methods: The CLIMA (Clinical Phenotypes in Actual Clinical Practice) study was an observational, cross-sectional investigation involving twenty-four sites evenly distributed throughout Italy. Patients were tentatively grouped based on their history and claimed prevailing symptoms at recruitment: chronic cough (CB, suggesting chronic bronchitis); dyspnoea (possible emphysema components, E); recurrent wheezing (presuming asthma components, A). Variables collected were: anagraphics; smoking habit; history of asthma; claim of >1 exacerbations in the previous year; blood eosinophil count; total blood IgE and alpha1 anti-trypsin (α1-AT) levels; complete lung function, and the chest X-ray report. mMRC, CAT, BCS, EQ5d-5L were also used. The association between variables and phenotypes were checked by Chi-square test and multinomial logistic regression.
Results: The CB phenotype was prevalent (48.3%), followed by the E and the A phenotypes (38.8% and 12.8%, respectively). When dyspnea was the prevailing symptom, the probability of belonging to the COPD-E phenotype was 3.40 times higher. Recurrent wheezing was mostly related to the COPD-A phenotype. Lung function proved more preserved in the COPD-CB phenotype. Smoke; n. exacerbations/year; VR, and BODE index were positively correlated with the COPD-E phenotype, while SpO₂, FEV1/FVC, FEV1/VC, and FEV1 reversibility were negatively correlated. Lower DLco values were highly probative for the COPD-E phenotype (p<0.001). Conversely, smoke, wheezing, plasma eosinophils, FEV1 reversibility, and DLco were positively correlated with the COPD-A phenotype. The probability of belonging to the COPD-A phenotype raised by 2.71 times for any increase of one unit in % plasma eosinophils (p<0.001). Also multiparametrical scores contributed to discriminate the three phenotypes.
Conclusion: the recognition of the main phenotypes of COPD can be effectively pursued by means of a few clinical and instrumental parameters, easy to obtain also in current daily practice. The phenotypical approach is crucial in the management of COPD as it allows to individualize the therapeutic strategy and to obtain more effective clinical outcomes

Author Biography

on behalf of the CLIMA Study Group*

R.W. Dal Negro, Centro Nazionale Studi di Farmacoeconomia e Farmacoepidemiologia Respiratoria, Verona; M. Carone, Fondazione S. Maugeri, Cassano delle Murge (BA); G. Cuttitta, IBIM-CNR, Palermo; L. Gallelli, Azienda Ospedaliera-Universitaria Mater Domini, U.O. Farmacologia, Catanzaro; M. Pistolesi, Azienda Ospedaliera Universitaria Careggi - Pneumologia e Fisiopatologia Toraco-Polmonare, Firenze; S. Privitera, C.P.M., Giarre, Catania; P. Ceriana, IRCCS ICS Maugeri, Clinica del Lavoro e della Riabilitazione, Pavia; P. Pirina, U.O. di Pneumologia, Azienda Ospedaliera Universitaria, Sassari; B. Balbi, Unità Operativa di Pneumologia Riabilitativa, IRCCS ICS Maugeri, Istituto di Veruno, Novara; C. Vancheri, Pneumologia Riabilitativa, Azienda Ospedaliera Universitaria Policlinico, Vittorio Emanuele, Catania; F.M. Gallo, SSD Pneumologia Territoriale, Azienda Sanitaria Locale, Matera; A. Chetta, Clinica Pneumologica, Azienda Ospedaliera Universitaria-Ospedale G. Rasori, Parma; S. Baglioni, S.C. Pneumologia, Azienda Ospdealiera, Perugia; C. Bucca, AOU Molinette, SCDU Pneumologia, Torino; F. Mazza, S.C. Pneumologia, Azienda per l’Assistenza Sanitaria n. 5, Friuli Occidentale, Pordenone; A. Melani, Policlinico S. Maria alle Scotte, Ambulatorio Fisiopatologia Respiratoria, Siena; A. Sanna, U.O. di Pneumologia, Ospedale Civile, Pistoia; M. Latorre, Presidio Ospedaliero delle Apuane. U.O. Pneumologica, Massa-Carrara; C. Micheletto, Azienda U.L.S.S. n. 21, UOC di Pneumologia, Legnago (VR); S. Marinari, Ospedale Policlinico SS. Annunziata, Divisione di Pneumologia, Chieti; F. De Blasio, Casa di Cura Clinic Center, Pneumologia, Napoli; S. Bellofiore, Presidio Ospedaliero A.O.U., Policlinico Vittorio Emanuele di Catania, Chirurgia Toracica Padiglione M1, Catania; P. Turco, Research & Clinical Governance, Verona, Italy.

References

Fletcher CM, Peto R. The natural history of chronic airflow obstruction. Br Med J 1977;1:1645-8.

Mannino DM, Higuchi K, Yu TC, Zhou H, Li Y, Tian H, Suh K. Economic burden of chronic obstructive pulmonary disease by presence of comorbidities. Chest 2015;147:199-201.

Dal Negro RW, Celli BR. Patient Related Outcomes-BODE (PRO-BODE): A composite index incorporating health utilization resources predicts mortality and economic cost of COPD in real life. Respir Med 2017;131:175-8.

Dal Negro RW. COPD: The annual cost-of-illness during the last two decades in Italy, and its mortality predictivity power. Healthcare 2019;7:35.

Snider GL. Chronic obstructive pulmonary disease: A definition and implications of structural determinants of airflow obstruction for epidemiology. Am Rev Respir Dis 1989;140:S3-8.

Fabbri LM, Romagnoli M, Corbetta L, Casoni G, Busljetic K, Turato G, et al. Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003;167:418-24 .

Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:2645-53.

Han MK, Agusti A, Calverly PM, Celli BR, Criner G, Curtis JL, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med 2010;182:598-604.

Global initiative for Chronic Obstructive lLung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Accessed: March 30, 2015. Available from: http://www.goldcopd.org/uploads/users/files/GOLD_Report_2015_feb18.pdf

Soriano JB, Davis KJ, Coleman B, Visick G, Mannino D, Pride NB. The proportional Venn diagram of obstructive lung disease: Two approximations from the United States and the United Kingdom. Chest 2003;124:474–81.

Marsh SE, Travers J, Weatherall M, Williams MV, Aldington S, Shirtcliffe PM, et al. Proportional classifications of COPD phenotypes. Thorax 2008;63:761-7.

Segreti A, Stirpe E, Rogliani P, Cazzola M. Defining phenotypes in COPD: an aid to personalized healthcare. Mol Diagn Ther 2014;18:381-8.

Sheikh K, O Coxon H, Parraga G. This is what COPD looks like. Respirology 2016;21:224-36.

Rogliani P, Ora J, Puxxeddu E, Cazzola M. Airflow obstruction: is it asthma or is it COPD? Intern J COPD 2016;11:3007-13.

Calle Rubio M, Casamor R, Miravitlles M. Identification and distribution of COPD phenotypes in clinical practice according to Spanish COPD Guidelines: The FENEPOC study. Int J Chron Obstruct Pulmon Dis 2017;9;12:2373-83.

Beeh KM, Kornmann O, Beier J, Ksoll M, Buhl R. Clinical application of a simple questionnaire for the differentiation of asthma and chronic obstructive pulmonary disease. Respir Med 2004;98:591–7.

Gibson PG, Simpson JL. The overlap syndrome of asthma and COPD: What are its features and how important is it? Thorax 2009;64:728-35.

Zeki AA, Schivo M, Chan A, Albertson TE, Louie S. The asthma-COPD overlap syndrome: A common clinical problem in the elderly. J Allergy 2011;2011:861926.

Sobradillo P, Garcia-Aymerich J, Agusti A. Clinical phenotypes of COPD. Arch Bronchopneumol 2010;46:s8-11.

Vestbo J. COPD: definition and phenotypes. Clin Chest Med 2014;35:1-6.

Polverino F, Sam A, Guerra S. COPD: to be or not to be, that is the question. Am J Med 2019;132:1271-8.

Fragoso E, André S, Boleo-Tomè JP, Arelas V, Munha J, Cardoso J. Understanding COPD: a vision on phenotypes, comorbidities and treatment approach. Rev Port Pneumol 2016;22:101-11.

Siafakas N, Corlateanu A, Fouka E. Phenotyping before starting treatment in COPD? COPD 2017;14:367-74.

Segal LN, Martinez FJ. Chronic obstructive pulmonary disease subpopulations and phenotyping. J Allergy Clin Immunol 2018;141:1961-71.

Snider GL. What's in a name? Names, definitions, descriptions, and diagnostic criteria of diseases, with emphasis on chronic obstructive pulmonary disease. Respiration 1995;62:297-301.

Pinto LM, Alghamdi M, Benedetti A, Zaihara T, Landry T, Bourbeau J. Derivation and validation of clinical phenotypes for COPD: a systematic review. Respir Res 2015;16:50.

Koblikek V, Milienkovic B, Barczyk A, Tkacova R, Somfay A, Zykov K, et al. Phenotypes of COPD patients with a smoking history in Central and Eastern Europe: the POPE Study. Eur Respir J 2017;49:1601446.

Ciai C-S, Liam C-K, Pang Y-K, Ng DL-C, Tan S-B, Wong T-S, Sia J-E. Clinical phenotypes of COPD and health related quality of life: a cross sectional study. Intern J COPD 2019;14:565-73.

Gut-Gobert C, Cavailles A, Dixmier A, Guiollot S, Joneau S, Leroyer C, et al. Women and COPD: do we need more evidence? Eur Respir Rev 2019;28:180055.

Green RH, Brightling CE, Bradding P. The reclassification of asthma based on subphenotype. Curr Opin Allergy Clin Immunol 2007;7:43-50.

Putcha N, Fawzy A, Matsui EC, Liu MC, Bowler RP, Woodruff PG, et al. Clinical phenotypes of atopy and asthma in COPD: A meta-analysis of SPIROMICS and COPD gene. Chest 2020;158:2333-45.

Hurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 2010;363:1128-38.

Skold CM. Remodeling in asthma and COPD - differences and similarities. Clin Respir J 2010;4:s20-7.

Singh D, Kolsum U, Brightling CE, Locantore N, Agusti A, Tal-Singer R, et al. Eosinophilic inflammation in COPD: prevalence and clinical characteristics. Eur Respir J 2014;44:1697-700.

No authors listed. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995;152:S77-121.

Miravitlles M, Calle M, Soler-Cataluña JJ. Clinical phenotypes of COPD: identification, definition and implications for guidelines. Arch Bronconeumol 2012;48:86-98.

Macklem PT, Mead J. Resistance of central and peripheral airways measured by a retrograde catheter. J Appl Physiol 1967;22:395-401

Lange P, Halpin DM, O’Connell DE, MacNee W. Diagnosis, assessment, and phenotyping of COPD beyond FEV1. Inter J Chron Obstruct Pulmon Dis 2016;11 3-12.

Jones PW. Health status measurement in chronic obstructive pulmonary disease. Thorax 2001;56:880-7.

Sciurba FC. Physiological similaritiesand differencs between COPD and asthma. Chest 2004;126:117s-24.

Puente-Maestu L, Stringer WW. Hyperinflation and its management in COPD. Inter J Chron Obstruct Pulmon Dis 2006;1:381-400.

Janson C, Malinovschi A, Amaral AFS, Accordini S, Bousquet J, Buist AS, et al. Bronchodilator reversibility in asthma and COPD: findings from three large population studies. Eur Respir J 2019;54:1900561

Vazquez JH, Garcia IA, Meca AA, de Andres AL, Ruix CM, Garcia MJB, et al. COPD phenotypes: differences in survival. Inter J Chron Obstruct Pulmon Dis 2018;13:2245-51.

Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 2004;350:1005-12.

Jones PW, Brusselle G, Dal Negro RW, Ferrer M, Kardos P, Levy ML, et al. Health-related quality of life in patients by COPD severity within primary care in Europe. Respir Med 2011;105: 57-66.

Dal Negro RW, Bonadiman L, Turco P, Tognella S, Iannazzo S.- Costs of illness analysis in Italian patients with chronic obstructive pulmonary disease (COPD): an update. Clinicoecon Outcomes Res 2015;7:153-9

Barnes PJ. Against the Dutch hypothesis: asthma and chronic obstructive pulmonary disease are distinct diseases. Am J Respir Crit Care Med 2006;174:240-4.

Kraft M. Asthma and chronic obstructive pulmonary disease exhibit common origins in any country. Am J Respir Crit Care Med 2006;174:238-40.

Corlateanu A, Mendez Y, Wang Y, de Jesus Avendano Garnica R, Botnaru V, Siafakas N. Chronic obstructive pulmonary disease and phenotypes: a state-of-the-art. Pulmonology 2020;26:95-100.

Milanese M, Viegi G, Sposato B, Dal Negro RW. Respiratory function testing in the era of precision medicine. Clin Respir Med 2020;2:1009.