To the Editor: One of the most important causes of morbidity and mortality after hematopoietic stem cell transplantation (HSCT) is bronchiolitis obliterans (BO), which sometimes leads to irreversible and progressive air flow obstruction (AFO).^1-3 Usually this complication is seen after allogeneic transplantation in up to 26% of cases.4 The usual diagnostic method is spirometry. Other modalities are high resolution computed tomography (HRCT) and lung biopsy. The most well known and consistent risk factor for BO is chronic graft-versus-host disease (GVHD).^4,5

This cross-sectional study was carried out at the Shariati Hospital, Hematology, Oncology and Stem Cell Transplantation Research Center to compare diagnostic methods and to determine additional risk factors by two diagnostic methods. The patients who had allogeneic HSCTs at least six months previously were included in the study and followed from January to June 2009. Exclusion criteria were current smoking or a history of smoking, history of asthma, chronic obstructive pulmonary disease or bronchiectasis, transplantation more than one time and abnormal spirometry with an FEV₁/FVC less than 70%. All of the patients underwent spirometry and chest HRCT in the inspiratory and expiratory phase. Spirometric criteria for diagnosis of bronchiolitis obliterans without consideration of the age of the patient is defined as FEV1/FVC less than 75% or a more than 10% decrement of FEV1/FVC from the baseline value. HRCT criteria were air trapping or a mosaic pattern, which is exaggerated on expiratory views. A diagnosis of bronchiolitis obliterans requires one of the spirometric or imaging criteria.

Forty-two patients completed the study. Nineteen (45.2%) met the diagnostic criteria for BO, but only 11 (26.2%) had abnormal spirometry and 17 (40.5%) patients had air trapping and a mosaic pattern in the chest HRCT that was compatible with a diagnosis of BO. Eleven (26.2%) patients had a history of acute GVHD and 21 (50%) had a history of chronic GVHD. Only 10 (23.8%) had no history of acute or chronic GVHD. There was a statistically meaningful correlation between BO and GVHD (P=.037); only one case of BO was in the non-GVHD group (10%), 6 cases in the acute GVHD group (54.5%) and 12 cases were in the chronic GVHD group (57.1%). Ten patients (23.8%) were less than 20 years old, 22 were in the 21-40 year-old group (52.4%) and 10 patients (23.8%) were older than 41 years.

Patient age seemed an independent risk factor for BO because the age range of 21-40 years had a 22.6 times greater chance of developing BO than those patients younger than 20 years old (odds ratio=22.6, 95% CI: 1.8-277.9 P=.015) and the older group (41-60 years) had a 16.6 times risk of developing BO compared with youngest group (OR=16.6, 95% CI: 1.1-246.8, P=.041).
Donor-recipient was a risk factor for BO (P=.037). More BO was seen in male recipients with female donors, which was expected, but interestingly the negative predictive value of symptoms (cough, sputum, dyspnea) in the age group under 20 years was 100%, compared with 80% in the middle group and 75% in the oldest group, which indicates that patients under 20 years old need screening for BO if they are asymptomatic. The second point we want emphasize is that spirometry is used for diagnosis of BO alone in most studies. The correlation of the two diagnostic methods in this study was 48%, but HRCT had a better diagnostic yield alone and fewer patients will be missed when screening by this method.

Dr. Gohari Moghadam (pulmonologist) did procedures and interpretation of results, and was also involved in writing. Bahareh Marghoob, resident in internal medicine was involved in case selection, arrangement of patients for procedures, analysis of data and writing of paper. Kamran Alimoghaddam (hematologist oncologist) participated in HSCT and interpretation of data and writing of the paper. Shapour Shirani (radiologist) was involved in CT scanning of patients and interpretation of data. Dr. Ghavamzadeh (head of HSCT department) participated in HSCT.

References

1. Ostrow D, Buskard N, Hill RS, Vickarsc D, Churg A. Bronchiolitis complicating bone marrow transplantation. Chest. 1985;87:828-830.
2. Epler GR, Colby TV. The spectrum of bronchiolitis oblitertans. Chest. 1983;83:161-162.
3. Marras TK, Szalai JP, Chan CK, Lipton JH, Messner HA, Laupacis A. Pulmonary function abnormalities after allogeneic marrow transplantation : a systematic review and assessment of an existing predictive instrument. Bone Marrow Transplant. 2002;30:599-607.
4. Chien JW, Martin PJ, Gooley TA, Flowers ME, Heckbert SR, Nichols WG. Air flow obstruction after myeloablative allogeneic hematopoietic stem cell transplantation. Am J Resp Critic Care Med. 2003;168:208-214.
5. Chien JW, Martin PJ, Flowers ME, Nichols WG, Clark JG. Implications of early airflow decline after myeloablative allogeneic stem cell transplantation. Bone Marrow Transplant. 2004;33:759-764.