Characterisation and prognosis of undiagnosed chronic obstructive pulmonary disease patients at their first hospitalisation

Chronic obstructive pulmonary disease (COPD) represents a major public health problem, and its mortality and disability burden is expected to rise in the coming decades [1, 2]. Nonetheless, the majority of studies from general population and primary care have detected that a high proportion of individuals fulfilling COPD diagnosis criteria remain undiagnosed [3‐9]. Interestingly, it has been reported that a high proportion of undiagnosed patients already suffer from respiratory symptoms [7, 8]. A recent population-based study demonstrated that even newly diagnosed COPD patients with mild airflow limitation exhibit a significant impairment in their health-related quality of life and certain activities of daily living, when compared with individuals without COPD [9]. Therefore, both researchers and practitioners advocate for early detection strategies aimed at reducing COPD burden through proven health-care interventions [10].

There is a lack of specific information regarding COPD under-diagnosis in patients requiring hospitalisation because of an exacerbation of the disease. Two previous studies in a hospital setting highlighted that one-third of patients had never been diagnosed or treated. One of these studies involved patients who went to the emergency room for COPD exacerbation, and the second study was a small retrospective study of patients admitted to the hospital for the first time for a COPD exacerbation [11, 12]. The current study describes the characteristics of COPD patients who were undiagnosed at the time of their first hospital admission because of a COPD exacerbation and their short- and long-term outcomes.

This study has three main findings: (1) undiagnosed patients (34% of all patients hospitalised for the first time because of an exacerbation of COPD) have milder airflow limitation, fewer symptoms, fewer comorbidities, and better HRQL when compared with patients with a previous diagnosis of COPD; (2) establishing a COPD diagnosis is associated with a positive short-term effect on smoking cessation; and (3) undiagnosed patients have a lower risk of re-hospitalisations but a similar mortality after hospitalisation when adjusted for severity of illness and covariates.

A high prevalence of COPD under-diagnosis has been frequently reported, both in population based-studies and in primary care settings [3‐9]. In contrast, there is little information available regarding COPD under-diagnosis in hospitalised patients. Our study confirms that undiagnosed COPD is not confined to the general population or primary care. We determined that one-third of patients admitted for the first time for a COPD exacerbation were undiagnosed. This finding is in accordance with a previous Italian study of patients attending the emergency room because of a COPD exacerbationand a retrospective study of patients admitted in a UK hospital for the first time for a COPD exacerbation [11, 12]. Importantly, the hospital-based design and the thorough characterisation of the patients in our study prevented the inclusion of healthy subjects with age-related airflow limitation.

The substantial differences observed between diagnosed and undiagnosed patients deserve special consideration. In our cohort, undiagnosed patients were younger, had less severe airflow limitation and a better HRQL. These findings confirm several previous population-based studies with similar observations [8, 9, 27]. In contrast, Zoia et al. did not find differences in age and severity based on previous COPD diagnosis in the hospital setting [11]; however, their diagnosed patients had more comorbidities when compared with undiagnosed patients [11]. It is possible that the lack of diagnosis (hence, treatment) may have resulted in an “earlier” first hospital admission for a COPD exacerbation, when the patient still had mild-to-moderate COPD [15]. In fact, our findings indicated that undiagnosed COPD may be related to a lack of primary care interventions prior to the first admission (Table 3). Unfortunately, specific information about these interventions, such as smoking cessation advice, was not recorded in the PAC-COPD study.

Similar to the report by Zoia et al., we identified a higher proportion of current smokers in the undiagnosed group when compared with the diagnosed group [11]. We also observed that the establishment of a COPD diagnosis was associated with a significant reduction in current smokers (Figure 2). This finding is similar to previous reports that showed that smokers with airflow limitation had significantly higher smoking cessation rates than those with normal spirometry [28, 29]. These data identify a potentially important window of opportunity for therapeutic intervention.

The re-hospitalisation rate was lower in newly diagnosed COPD patients following their first admission (Figure 3, panel A); however, this decreased risk was not significant after multivariable adjustments (Table 3), indicating that the protective effect of undiagnosed COPD was likely due to a lower severity of the disease. This interpretation is challenged by the lack of differences in mortality during follow-up (Figure 3, panel B), and a better prognosis is expected in undiagnosed patients with a milder disease. Thus, this observation requires further research. One potential explanation is that cardiovascular disease might play a more relevant role in undiagnosed patients because the majority were active smokers and had milder COPD. This idea is supported by previous studies that consistently showed the causes of death in patients with mild COPD were predominantly cancer and cardiovascular disease, while deaths due to respiratory disease became more common with increasing COPD severity [30]. In our study, there were very few deaths during follow-up. Therefore, the sample size was too small to analyse differences in cause of death between groups.

Clinical features and outcomes of newly diagnosed COPD patients highlighted the clinical relevance of pursuing a correct diagnosis in all hospitalised patients and applying the appropriate corresponding health measures. A recent report by Suissa et al.[31] identified two strategic targets for the management of COPD patients during their first hospitalisation. First, the second hospitalisation should be delayed as much as possible because subsequent exacerbations increase exponentially in frequency and intensity. Second, improved treatment is needed to reduce early mortality [31].

Some limitations of our study should be addressed. Firstly, self-reported information about COPD diagnosis rather than objective medical records could lead to misclassification. Secondly, the very small number of undiagnosed patients with very severe COPD has limited our analysis with regard to this specific subgroup. Finally, our results regarding the extent of COPD under-diagnosis and the clinical profile of these patients may not be able to be generalised to other health care systems; however, the effect of the lack of COPD diagnosis on subsequent hospitalisations and mortality are likely to be generally applicable.

The strengths of our study included the large cohort of COPD patients, and their homogeneity with respect to incipient COPD hospitalisations, the wide spectrum of disease severity, and length of follow up. Furthermore, the comprehensive multidimensional assessment used in our study allowed adjustments for potential confounders.

This study showed that approximately one-third of patients hospitalised for the first time because of a COPD exacerbation had not been previously diagnosed (hence, treated). In addition, patients generally exhibited less severe disease, and their risk of re-hospitalisation was lower when compared with patients who were hospitalised with an established COPD diagnosis. First admission due to COPD exacerbation provides a window of opportunity for early treatment, in particular for smoking cessation intervention.

The “Phenotype and Course of COPD (PAC-COPD)” Study Group: Centre for Research in Environmental Epidemiology (CREAL), Barcelona: Josep M Antó (Principal Investigator), Judith Garcia-Aymerich (project coordinator), Marta Benet, Jordi de Batlle, Ignasi Serra, David Donaire-Gonzalez, Stefano Guerra; Hospital del Mar-IMIM, Barcelona: Joaquim Gea (centre coordinator), Eva Balcells, Àngel Gayete, Mauricio Orozco-Levi, Ivan Vollmer; Hospital Clínic-Institut D’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona: Joan Albert Barberà (centre coordinator), Federico P Gómez, Carles Paré, Josep Roca, Robert Rodriguez-Roisin, Xavier Freixa, Diego A Rodriguez, Elena Gimeno-Santos, Karina Portillo; Hospital General Universitari Vall D’Hebron, Barcelona: Jaume Ferrer (centre coordinator), Jordi Andreu, Esther Pallissa, Esther Rodríguez; Hospital de la Santa Creu i Sant Pau, Barcelona: Pere Casan (centre coordinator), Rosa Güell, Ana Giménez; Hospital Universitari Germans Trias i Pujol, Badalona: Eduard Monsó (centre coordinator), Alicia Marín, Josep Morera; Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat: Eva Farrero (centre coordinator), Joan Escarrabill; Hospital de Sabadell, Corporació Parc Taulí, Institut Universitari Parc Taulí (Universitat Autònoma de Barcelona), Sabadell: Antoni Ferrer (centre coordinator); Hospital Universitari Son Dureta, Palma de Mallorca: Jaume Sauleda (centre coordinator), Àlvar G Agustí, Bernat Togores; Hospital de Cruces, Barakaldo: Juan Bautista Gáldiz (centre coordinator), Lorena López; Hospital General Universitari, València: José Belda.