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Long-term Outcome and Lung Cancer Incidence in Patients With Hemoptysis of Unknown Origin^*

^* From the Department of Endoscopy (Drs. Herth and Becker), Thoraxklinik, Heidelberg, Germany; and Division of Pulmonary and Critical Care Medicine (Dr. Ernst), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

Correspondence to: Armin Ernst, MD, FCCP, Director, Interventional Pulmonology, Beth Israel Deaconess Medical Center, West Campus, One Deaconess Rd, Boston, MA 02115 e-mail: aernst{at}caregroup.harvard.edu

	Abstract

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Study objective: To provide current data on the long-term outcome and incidence of lung cancer in a large cohort of patients with hemoptysis of unknown origin.

Design: A retrospective chart review followed by a telephone interview for follow-up.

Setting: A university-affiliated tertiary referral center for pulmonary diseases.

Patients: Seven hundred twenty-two patients who presented with hemoptysis from January 1990 to December 1993. One hundred thirty-five patients were identified as having hemoptysis of unknown origin.

Results: One hundred thirty-five patients (19%) had hemoptysis of unknown origin; follow-up data were obtained in 115 patients, of whom 100 were still alive. The mean time of observation was 6.6 years after initial presentation. Lung cancer developed in 7 of 115 patients (6%) and was unresectable once detected; all of these patients were smokers > 40 years old, and malignancy developed within 3 years after first presentation.

Conclusions: Hemoptysis of unknown origin is present in a minority of patients presenting with hemoptysis if evaluated at a referral center for pulmonary diseases. Lung cancer seems to be increasing in these patients compared to previous studies, and closer follow-up or additional testing may be indicated in the defined population at risk.

Key Words: bronchoscopy • diagnosis • hemoptysis • lung cancer

	Introduction

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Hemoptysis is a common indication for referral to pulmonologists and bronchoscopy. The symptom is distressing for the patient and frequently raises concerns about underlying malignancies. The detection rate of the source of bleeding varies from 30 to 80% despite adequate workup.^{1 2 3 4 5}

In 1952, Douglass and Carr⁶ used the term "idiopathic hemoptysis" to describe bleeding without an established cause after medical evaluation and bronchoscopy. In older studies,^{6 7} it was suggested that the incidence of lung cancer in this population is low, and close follow-up has not been advocated. As lung cancer has become a disease of epidemic proportions in countries with a high incidence of tobacco use, we were interested to see if this remains the case. We present our data on long-term follow-up in a large cohort of patients with hemoptysis of unknown origin.

	Materials and Methods

TOP Abstract Introduction Materials and Methods Results Discussion References

 
A retrospective chart review was performed on all patients who were referred to the pulmonary department for evaluation of hemoptysis between January 1990 and December 1993. Workup and results were reviewed. All patients underwent careful bronchoscopic evaluation of the tracheobronchial tree and chest radiography. A chest CT was performed at the discretion of the evaluating pulmonary physician. All bronchoscopic examinations were performed with a fiberoptic instrument in standard fashion. Endobronchial and transbronchial biopsies were performed when indicated, and all specimens were routinely examined for cytology and microbiology.

Hemoptysis of unknown origin was defined as endoscopic examination and imaging study findings and no significant abnormalities found on all submitted specimens. Radiologists read all radiographic studies.

All patients with hemoptysis of unknown origin were identified, and follow-up data were obtained in that patient population by contacting the family physician or the patient directly by telephone. Information obtained included current smoking habits and newly developed pulmonary or nonpulmonary disorders possibly linked to hemoptysis. A cohort study analysis for unpaired differences was performed to assess for statistical differences between the identified groups.

	Results

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Within the reviewed period, 722 patients were evaluated for hemoptysis and all charts were available for review (Table 1 ). Four hundred eight-seven patients (67%) were men, and 235 patients (33%) were women. The mean age was 46.7 years (SD, 13.6; range 20 to 81 years). Four hundred forty patients (61%) were classified as smokers. A clinical diagnosis of COPD was present in 213 patients (30%).

At the time of the initial workup, all patients underwent physical examination, basic laboratory testing, chest radiography, and bronchoscopy. During bronchoscopy, bleeding could be localized to the segmental level in 29 patients. In 36 patients, localization to the left or right side of the tracheobronchial tree was possible. Forty-eight patients did have blood in the airway, but no localization was possible. In 22 patients, no blood was visible during the examination. In all patients, material was sent for acid-fast bacilli smear and culture, microbiology, and cytology studies. No significant positive findings were noted.

Follow-up data were obtained in 115 patients (85%; Table 3 ), and no follow-up data were available for 20 patients. Of the 115 patients with data available, 76 patients were men and 39 patients were women, with a mean age of 48.3 years (range, 21 to 82 years). The mean time of observation between initial assessment and follow-up was 6.6 years (SD, 1; range, 4.7 to 8.3 years).

Of the 115 patients, lung cancer developed in 7 patients (6%) in the interim (non-small cell lung cancer in 6 patients, and small cell lung cancer in 1 patient). All seven patients (six men and one woman) were smokers, and the cancer developed within the first 3 years after the initial workup. Their mean age was 49.7 years (range, 43 to 61 years). The mean time between initial evaluation for hemoptysis and the eventual diagnosis of lung cancer was 17.3 months (SD, 7.5; range, 9 to 23 months).

Using the cohort study analysis for unpaired differences, a 10% probability was found for lung cancer developing after hemoptysis of unknown origin if the patient is a current smoker and > 40 years old. Of the 100 patients who were still alive, only 9 patients had recurrent hemoptysis. All patients underwent another full evaluation including bronchoscopy, but a diagnosis could not be established

	Discussion

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Hemoptysis remains a distressing symptom and, at times, a challenging diagnostic problem. Clear guidelines for the initial workup and follow-up in patients without a definitive diagnosis are missing. Mostly, this appears to be due to a lack of current available data and follow-up in large groups. The etiology for hemoptysis may vary depending on geographic location, and infections such as tuberculosis play a significant role in developing countries.^{8 9} In many countries, malignancies are the leading diagnosis and concern, as is the case in our population.

In our study, we could demonstrate that in the majority of patients a definitive diagnosis could be made, if the patient is referred to an experienced referral center for pulmonary diseases. The workup in all patients included a bronchoscopic examination, which is important to note, as a significant number of patients with newly diagnosed lung cancer had normal imaging study findings. The leading diagnosis at the time of initial workup was a malignant process, closely followed by exacerbation of underlying chronic obstructive disease.

Other studies have looked at the outcomes of patients with hemoptysis of unknown origin. The percentage of this patient population in some studies is fairly high, as fewer patients have a definitive diagnosis made at the time of presentation, and can range up to 30%,^{10 11 12} compared to 19% in our population. Previously, a good prognosis and small likelihood of lung cancer developing was suggested in these patients. In a study from 1952,⁶ lung cancer developed in only 1 of 55 patients. In 1960,⁷ none of 97 patients had lung cancer develop within 1 year. Lung cancer has become a disease of epidemic proportions since that time. This could explain, in part, our findings that lung cancer developed in 7 of 115 patients despite unrevealing bronchoscopy and normal chest radiographic findings at the initial presentation. We also followed a larger patient population for a longer period of time. Unfortunately, none of the patients with lung cancer was resectable at the time of diagnosis. This could be due to the fact that no routine follow-up was performed.

All of the patients in whom lung cancer developed after hemoptysis of unknown origin were smokers > 40 years of age, and the lung cancer developed within 3 years. This is a fairly distinct population, and more routine follow-up could be considered for these patients. Further studies are needed to see if such an approach could lead to better outcomes for these patients, and to determine what roles newer imaging technologies, such as positron emission tomography scanning and autofluorescense bronchoscopy, may play. It remains encouraging that a life-threatening malignancy will not develop in the majority of patients after an unexplained episode of hemoptysis, even after long-term follow-up.

Received for publication February 6, 2001. Accepted for publication May 2, 2001.

	References

TOP Abstract Introduction Materials and Methods Results Discussion References

 

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8. Head, JR, Moen, CW (1949) Late nontuberculous complications of calcified hilus lymph nodes. Am Rev Tuberc 60,1[Medline]
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