Haemoptysis in adults: a 5-year study using the French nationwide hospital administrative database

Discussion

This 5-year retrospective study is, to our knowledge, the first to analyse haemoptysis, its aetiologies and outcomes in the population of a whole country, France. We found that haemoptysis accounted for 0.2% of hospitalised patients. In this high-income country, we showed that the most frequent aetiologies were respiratory infections, lung cancer and bronchiectasis. We also demonstrated that haemoptysis of unknown origin accounted for a large percentage of cases. A significant proportion of these were associated with the development of lung cancer during follow-up. Finally, haemoptysis is a symptom that portends a bleak outcome, as the 3-year mortality rate was 20%.

The main limitation of the present study was the coding system, which may have induced some inaccuracies. The results may have been biased by coding mistakes or omissions, which may have led to the under- or overestimation of both incidence and aetiologies. Moreover, the code for haemoptysis may have been recorded more often in cases requiring substantial amounts of care and as a result we may have over-selected serious cases of haemoptysis. The initial high percentage (almost 50%) of cryptogenic haemoptysis may also be overestimated, and may result from inaccurate coding. However, as the frequency of haemoptysis found in our study correlates with previous studies, we feel that such inaccuracies may not be considerable. Indeed, recent studies that investigated the reliability of PMSI data by comparing them with reference data from other sources, including a stroke registry, a perinatal survey and vaccine safety assessments, showed that PMSI data can be reliably used for epidemiological purposes [10–13].

In the present work, the incidence of haemoptysis varied during the year and confirmed the results of other studies, which found two peaks, one in March and one in October [4]. Seasonal variations in the incidence of vascular diseases and overall mortality have already been demonstrated [17–20]. The main hypothesis to explain these very reproducible variations is the infectious origin of a high percentage of haemoptysis cases. Other hypotheses, such as hypertensive crises due to cold weather, variations in metabolism, the intake of vitamin C and variations in atmospheric pressure have been put forward [17–20].

Mortality rates in our study were substantial. Our results concerning in-hospital mortality (7% when deaths from lung cancer were excluded) during the first episode of haemoptysis did not differ from those in other studies [1, 5, 21]. The mortality rates in the subgroup of haemoptysis of unknown origin were similar, suggesting that the lack of a described aetiology at the initial evaluation was not a distinct risk factor for increased mortality in our study. However, some deaths could have been due to lung cancer. Nonetheless, 20% of patients, with the exclusion of lung cancer patients, died during the 3 years of follow-up. These results are probably underestimated because the studied mortality concerned in-hospital mortality only. Few studies have focused on the follow-up of patients with haemoptysis. Among these, one French prospective study of 39 chronic obstructive pulmonary disease (COPD) patients presenting with cryptogenic haemoptysis found a mortality rate of 2.6% at 5 years [22]. A North American retrospective study of patients with cryptogenic haemoptysis found a 5-year mortality rate of 9.1% [23]. The observed differences are probably due to the small number of highly selected patients in the former study [22], which may have led to an underestimation of overall mortality. Herth et al.[9] found a mortality rate of 13% after 6 years. All of the patients in the Herth et al. study died from the evolution of underlying diseases such as COPD, lung cancer, cirrhosis and granulomatous polyangiitis. Although we suspect that mortality in our study may have been related to underlying conditions rather than haemoptysis per se, the PMSI database did not allow us to make such distinctions.

In the present work, lower respiratory tract infection was the main cause of haemoptysis. These results tally with a retrospective study from Israel [5], although the proportion of respiratory infections was lower in our study (34% versus 23%, respectively). However, both studies suffer from the lack of an accurate definition of respiratory infections. In our study, clinicians were free to code “respiratory infections” in the absence of radiological documentation or bacteriological proof, which may have overestimated their incidence.

Pulmonary cancers were the second most frequent cause of haemoptysis, with an average incidence of 17.4%. These results are in keeping with the study by Hirshberg et al. [5] (19%), but differ from other studies. In a North American study, lung cancer accounted for 29% of cases [6]. In a South Korean study, Lee et al. [1] found lung cancers in 5.9% of their population of haemoptysis patients. These differences may be due to the higher incidence of tuberculosis, and therefore bronchiectasis, in Asia.

Haemoptysis as an adverse effect of anticoagulant therapy represented 4% of all haemoptysis cases in our study. As the codes for anticoagulants do not engender modifications in the budget allocated for the hospitalisation, this frequency may be underestimated. This rate is high compared with the results of other studies, although in many studies, this aetiology was not mentioned or analysed. Lee et al. [1] focused on haemoptysis in patients with bronchiectasis and found that anticoagulant and antiplatelet therapy did not increase the risk of bleeding in this population, whereas Savale et al. [2] found treatments predisposing to haemorrhage in 24% of their patients. It is difficult to determine whether such treatments are the real cause or a risk factor of haemoptysis. It would be interesting to know what treatments are associated with haemoptysis and, specifically, whether new anticoagulation treatments are more often associated with the symptom. The main adverse effects reported so far include gastrointestinal, cerebral and pericardial haemorrhage [24], but no studies have shown an increased risk of haemoptysis with these new treatments [24, 25]. Unfortunately, we were not able to study any association between the risk of haemoptysis and specific anticoagulant treatments, as the PMSI database does not allow the identification of the type of anticoagulant therapy used. There is no specific code for antiplatelet treatment in the PMSI database. Moreover, a number of cases of haemoptysis associated with anticoagulant or antiplatelet therapy were probably associated with the underlying pathologies and should be analysed with caution, particularly when haemoptysis recurs.

During follow-up in our study, 42.1% of recurrences were recorded as cryptogenic, and in 26.6% of these the recurrences were ultimately related to lung cancer. This could be explained by the high frequency of recurrent haemoptysis in lung cancer [26, 27].

Among patients with cryptogenic haemoptysis, 9.6% were diagnosed with lung cancer within the 3-year period of follow-up. However, we suspect that in a number of cases the initial haemoptysis was not cryptogenic and that clinicians were waiting for the results of pathology examinations before coding for lung cancer. In the literature, the mean delay between the first symptoms and the pathology results confirming lung cancer is between 20 days and 4 weeks [28, 29]. We therefore considered that lung cancer was the aetiology of the initial haemoptysis episode only when it was diagnosed within 2 months of the initial haemoptysis. In fact, a large proportion of these patients were diagnosed within 2 months of hospitalisation for haemoptysis, while another 4% of patients with cryptogenic haemoptysis were subsequently diagnosed with lung cancer during the long-term follow-up. Few studies have focused on the onset of lung cancer during the follow-up of patients with cryptogenic haemoptysis. In their retrospective study, Herth et al. [9] found that 6% of patients with cryptogenic haemoptysis developed lung cancer during the 3 years of follow-up. The rate increased to 10% in the subgroup of smokers aged >40 years.

In conclusion, ours is the first study to analyse the incidence and outcome of haemoptysis in the whole population of a country. Our results show that haemoptysis is still an ominous symptom. Indeed, a large proportion of haemoptysis cases had no clear aetiology and 4% were subsequently diagnosed with lung cancer during follow-up. Due to this significant incidence of lung cancer diagnosed during follow-up, we believe that there is a need for a dedicated follow-up of these patients to detect cancer at an earlier stage. The 3-year in-hospital mortality rate, excluding lung cancers, was very high (20%), and was probably more closely related to the underlying pathology than to haemoptysis itself.