ERJ Express. Published on May 28, 2015 as doi: 10.1183/09031936.00218214 ORIGINAL ARTICLE HAEMOPTYSIS IN ADULTS: A 5-YEAR STUDY

Haemoptysis in adults: a 5-year study using the French nationwide hospital administrative database Caroline Abdulmalak1, Jonathan Cottenet2, Guillaume Beltramo1, Marjolaine Georges1,3, Philippe Camus1,3,4, Philippe Bonniaud1,3,4,5 and Catherine Quantin2,3,4,5 Affiliations: 1Service de Pneumologie et Soins Intensifs Respiratoires, Centre Hospitalier Universitaire du Bocage, Dijon, France. 2Department of Medical Informatics, University Hospital, Dijon, France. 3Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France. 4INSERM U866, Dijon, France. 5Both authors contributed equally. Correspondence: Philippe Bonniaud, Service de Pneumologie et Soins Intensifs Respiratoires, Centre Hospitalier Universitaire du Bocage, 21079, Dijon, France. E-mail: [email protected]

ABSTRACT Haemoptysis is a serious symptom with various aetiologies. Our aim was to define the aetiologies, outcomes and associations with lung cancer in the entire population of a high-income country. This retrospective multicentre study was based on the French nationwide hospital medical information database collected over 5 years (2008–2012).We analysed haemoptysis incidence, aetiologies, geographical and seasonal distribution and mortality. We studied recurrence, association with lung cancer and mortality in a 3-year follow-up analysis. Each year, ∼15 000 adult patients (mean age 62 years, male/female ratio 2/1) were admitted for haemoptysis or had haemoptysis as a complication of their hospital stay, representing 0.2% of all hospitalised patients. Haemoptysis was cryptogenic in 50% of cases. The main aetiologies were respiratory infections (22%), lung cancer (17.4%), bronchiectasis (6.8%), pulmonary oedema (4.2%), anticoagulants (3.5%), tuberculosis (2.7%), pulmonary embolism (2.6%) and aspergillosis (1.1%). Among incident cases, the 3-year recurrence rate was 16.3%. Of the initial cryptogenic haemoptysis patients, 4% were diagnosed with lung cancer within 3 years. Mortality rates during the first stay and at 1 and 3 years were 9.2%, 21.6% and 27%, respectively. This is the first epidemiological study analysing haemoptysis and its outcomes in an entire population. Haemoptysis is a life-threatening symptom unveiling potentially life-threatening underlying conditions.

@ERSpublications Haemoptysis is ominous: there is often no clear aetiology and 4% of patients develop lung cancer during follow-up http://ow.ly/KqJDG

This article has supplementary material available from www.erj.ersjournals.com. Received: Nov 26 2014 | Accepted after revision: March 04 2015 Copyright ©ERS 2015

Eur Respir J 2015; In press | DOI: 10.1183/09031936.00218214

Copyright 2015 by the European Respiratory Society.

1

HAEMOPTYSIS | C. ABDULMALAK ET AL.

Introduction Haemoptysis is a symptom varying in its seriousness, and in most cases hospitalisation is required. A number of aetiologies are described in the literature. Prevalence differs depending on when the study was performed and the country of the study [1–8]. To the best of our knowledge, epidemiological studies conducted in high-income countries are old single-centre studies involving ∼100 patients. In a retrospective study in Israel [5], the main aetiologies were infectious respiratory disease (34%), followed by bronchiectasis (20%) and lung cancer (19%). In a study from South Korea [1], bronchiectasis was the main cause of haemoptysis (32.6% of cases) followed by tuberculosis (18.5%) and pulmonary fungal infections (10.8%). A French retrospective study that included >6000 patients [4] found that bronchial carcinoma accounted for 14.9% of cases and was the leading cause of haemoptysis. Haemoptysis of unknown origin, also called cryptogenic haemoptysis, is a critical issue as it accounts for 3–42% of all haemoptysis cases [4, 5]. The challenges of cryptogenic haemoptysis include missing a serious underlying condition such as lung cancer and the need to prevent the risk of recurrence if the initial cause is not correctly identified and treated. In a retrospective study, 6% of 135 patients [9] developed bronchial carcinoma during the follow-up of cryptogenic haemoptysis. In contrast, in a French prospective study of 81 patients with cryptogenic haemoptysis [2], no increased risk of lung malignancy was found. The objectives of our study were to provide an epidemiological update on haemoptysis in France, to assess outcomes in patients presenting with this symptom and to determine the benefit of close follow-up and extended investigations when first-line examinations are normal. The French national administrative database, also called the medicalisation of information system programme (PMSI) provides a huge amount of epidemiological information concerning hospitalised French patients [10–16]. Data pertaining to haemoptysis are reliable enough to count such patients and to describe the aetiologies of the condition.

Material and methods The national administrative database: PMSI Inspired by the American diagnosis-related groups model, the PMSI has gathered national administrative health data in France since 1991. The system was extended to all French healthcare facilities in 1997. The PMSI was initially designed to analyse the activities of hospitals and to contribute to the elaboration of strategic healthcare plans. Since 2008, each hospital’s budget has depended on the medical activity described in a specific programme which compiles discharge abstracts related to all admissions. Information in these abstracts is anonymous and covers both medical and administrative data. Diagnoses identified during hospital stays are coded according to the tenth edition of the International Classification of Diseases (ICD-10). Each facility produces its own standardised anonymous dataset which are then compiled at the national level. The fact that these national data are used to allocate hospital budgets has encouraged improvements in data quality in terms of coherence, accuracy and exhaustiveness. Population This study was a retrospective multicentre study based on nationwide PMSI data collected between January 2008 and December 2012. The use of the PMSI for this study was approved by the National Commission for Data Protection (CNIL 1576793). We included all patients aged >18 years who were admitted to hospital with haemoptysis during this period. All hospitalisations whose main or related or associated diagnosis was haemoptysis (ICD-10 code R042) were included. From the PMSI database, we collected data about age, sex, area of residence, reason for admission to hospital, related or associated diagnoses, month of discharge, length of stay, use of therapeutic embolisation, number of recurrences, time to recurrence and in-hospital mortality. We recorded data about the prevalence and incidence of haemoptysis in France. Prevalence corresponded to the number of patients presenting with haemoptysis during a period (recurrences during this period were excluded). Incidence was defined as the number of new cases per year. In the present work, we assumed that patients had not had haemoptysis during the previous year only. In fact, we were unable to identify events prior to the previous year. Prevalence and incidence data for each aetiological group (see below) were analysed. Variables In the PMSI coding system, the clinician must indicate the main diagnosis (symptom or disease) and any associated diagnoses (for conditions that require substantial levels of care). The related diagnosis could complete the main diagnosis when it corresponded to a Z-code (follow-up, treatments such as chemotherapy) and when a chronic disease could not be recorded during the hospitalisation. We therefore determined the potential aetiologies of haemoptysis when the diagnosis reported was the main, related or associated diagnosis. The aetiologies recorded were active pulmonary tuberculosis, pulmonary oedema, respiratory infection, mitral stenosis, broncho-pulmonary carcinoma, aspergillosis, pulmonary embolism, systemic disease (Goodpasture syndrome, micropolyangiitis, granulomatosis with polyangiitis and lupus),

2

DOI: 10.1183/09031936.00218214

HAEMOPTYSIS | C. ABDULMALAK ET AL.

the adverse effects of anticoagulants, bronchiectasis and cystic fibrosis, pulmonary hemosiderosis, chest trauma, airway foreign body, bronchial endometriosis, bronchial benign tumour and vascular malformation (fistula and aneurysm). A detailed list of the items that were recorded is available in online supplementary table S1. We studied the geographical distribution of haemoptysis in France to determine whether there were regional differences, and the seasonal distribution of haemoptysis. We studied long-term outcomes in patients with respect to recurrence, therapeutic embolisation and hospital mortality during 3 years of follow-up for patients admitted in 2008 and 2009, and 1 year of follow-up for patients admitted from 2008 to 2011. Recurrence was analysed according to the aetiology of the haemoptysis and the use of embolisation. Finally, all incident cases with none of the above aetiologies coded as the main/associated/ related diagnosis were recorded as cryptogenic haemoptysis. The frequency of the emergence of a disease (lung cancer, vasculitis or vascular malformation) was studied. Statistical analysis For bivariate analyses of qualitative variables, we used the Chi-squared test to compare percentages. Mean values of quantitative variables were compared using linear regressions. p-values