The Effect of Chemotherapy on the Pulmonary Function Tests in Cancer Patients with Healthy LungsCorrespondence Address :
Dr. Avjot K. Miglani
(Associate professor, (M.B.B.S, M.D) Physiology,
Punjab institute of medical sciences (PIMS), Jalandhar,
E-mail: email@example.com; Mob.: 07837744009
Aim: The present study was aimed at determining the effect of chemotherapy on lung function tests.
Material and Methods: This study was conducted on 35 cancer patients with healthy lungs, who undertook cancer chemotherapy. The pulmonary function test parameters, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1)and the FEV1/FVC ratio was recorded by using a computerized spirometer, Medspiror (Med Systems (P) Ltd.Chandigarh).
Results: All parameters showed a significant decline in the patients after the 1st and 2nd cycles of chemotherapy, as compared to those prior to the chemotherapy.
Conclusion: The present study confirms the fact that chemotherapeutic drugs have a toxic effect on lungs.
Chemotherapy pulmonary function tests
The incidence of respiratory illnesses has increased in the last 2-3 decades, thus leading to derangements of the lung functions, partly due to the increase in smoking, pollution, the life span and partly due to the use of various neoplastic drugs. At present, about 50% of the patients with cancer can be cured with chemotherapy, thus contributing to a cure in about 17% of the patients (1).
The ideal anticancer drugs can eradicate the cancer cells without harming the normal tissues, but unfortunately, no currently available agents meet this criterion and the pulmonary toxicity which is caused by the administration of chemotherapy is usually irreversible and progressive. So, the present study was undertaken to estimate the extent of damage which is done by anticancer drugs on the lungs.
The present study included 35 patients of either sex, who were diagnosed to have malignancy, but had healthy lungs. This study was conducted in the Department of Radiotherapy/Oncology, Shri Guru Teg Bahadur (S.G.T.B) Hospital, which is attached to the Government Medical College, Amritsar.
Patients with pulmonary metastasis and lung disease or those who had been previously exposed to radiotherapy during the treatment were excluded from the study.
All the subjects were explained about the procedures which were to be undertaken and written informed consent was taken from them as per the Helsinki declaration. This study was approved by the institutional ethics committee.
The patients were randomized into the following three groups : • Group I (1st visit) : before the start of chemotherapy. • Group II (2nd visit) : 3-4 weeks after the 1st visit(1st dose). • Group III (3rd visit) : 3-4 weeks after the 2nd visit(2nd dose).
Pulmonary function tests (PFT) were performed on the patients in the three groups at the baseline (before chemotherapy), 3-4 weeks after the start of chemotherapy and again, after the next3-4 weeks. The tests were done on a computerized spirometer, Medspiror (Med Systems (P) Ltd.Chandigarh), with the patients in a standing posture.
Recording of the PFTs
The relaxed subject in a standing position, were prepared to grip the sterile mouthpiece, as was demonstrated to him/her prior to the recording. When the subject was confident and familiar with the procedure, he/she was asked to perform a maximum inspiration after a deep expiration. The subject was then instructed to expire with maximum effort (maximum expiration).The mouthpiece was then removed and the following spirometric parameters were recorded for analysis.
1. Forced vital capacity (FVC): The maximum volume of air which expired after a maximum inspiration. 2. Forced expiratory volume in first second (FEV1): The fraction of vital capacity which expired during the 1st second of a forced expiration. 3. The FEV1/FVC ratio.
The data was collected, tabulated and analyzed by using the paired t-test for the comparison of the means and by the Chi-square test for the two-by-two tables. A ‘p’ value of 0.05 was takenas the cut off for the measure of significance.
The patients on whom the study was undertaken were on various chemotherapy regimens.
The mean age of the subjects in all the groups was 51.71+9.97 years (range 30 to 70 years).The number of male subjects was 13 and that of the female subjects were 22.
Forced Vital Capacity(FVC)Litres
The value of the FVC was higher in the group I cancer patients (before chemotherapy) in comparison to group II and group III cancer patients (after chemotherapy). The t-value which was calculated by comparing between group I and group II, was found to be 3.99 i.e highly significant. The FVC declined further in group III as compared to group I. The t-value was found to be 6.26, which showed that it was statistically highly significant (p <0.001).
Forced expiratory volume in the first second (FEV1)Litres
The difference in the value of the FEV1 in the group I cancer patients and group II patients was statistically highly significant, while the difference of its value between the group I and group III cancer patients was also statistically highly significant.
The FEV1/FVC ratio
The mean value of FEV1 as a percentage of FVC was found to be almost similar in all the three groups. The mean and standard deviation of FEV1/FVC in group I, group II and group III was 84.32+3.64, 85.67 + 4.48 and 85.11 + 5.15 respectively. The difference whatsoever was statistically at the cut off level of significance (p<0.05).The ratio of FEV1/FVC was more in favour of the restrictive pattern of lung disease.
In the present study, it was seen that the value of the FVC was high in the group I cancer patients (before chemotherapy) in comparison to the group II and group III patients (after chemotherapy). The FVC is a measure of the stroke volume if the lungs and thorax are regarded as a simple air pump. Any reduction in it will affect the ventilatory capacity. The causes of stroke volume reduction include pathologies such as fibrosis in the lung itself, which reduces its distensibility. The usual pulmonary injury with cytotoxic therapy is probably due to progressive pulmonary fibrosis, with relatively little of an inflammatory component and with a tendency to cause irreversible lung damage. Bleomycin and Mitomycin are cytotoxic antibiotics which cause pulmonary fibrosis in up to 5-10% of the patients (2), while the pulmonary toxicity from the combination of Gemcitabine and Paclitaxel is reported to be approximately 5% (3),(4). Several cytotoxic drugs that act by the alkylation of DNA have also been shown to cause alveolitis and pulmonaryfibrosis e.g. Busulphan, Chlorambucil, Cyclophosphamide (5) and Melphalan. These effects have also been seen with Methotrexate and Carmustine.
Similarly, the value of FEV1 was seen to decline significantly in the group II and group III patients, as compared to that in the group I patients. This decline is due to the toxic effects of chemotherapeutic drugs on lung functions. Many studies have shown similar results as those of this study.
The ratio of FEV1/FVC was more in favour of the restrictive pattern of the lung disorders.
We found a similarity in our findings with those of Jensen et al (6) (1990), who suggested that mantle-field irradiation was associated with a primary obstructive and minor restrictive lung function impairment, whereas chemotherapy and combined modality therapy was associated with a restrictive lung function impairment. Also, Nysom et al (7) (1998) who studied acute lymphoblastic leukemia patients, observed slight restrictive pulmonary disease which developed after the intake of chemotherapy.
Pulmonary toxicity is usually irreversible and progressive as a result of the administration of chemotherapy. The initial site of damage seems to be the endothelial cells with an inflammatory type reaction resulting in drug induced pneumonitis (2), (3). Another type of damage occurs as a result of an immunological mechanism, resulting in an allergic type reaction. Either the lung or the drug may act as an antigen in an allergic type reaction. Chronic exposure to chemotherapy causes extensive alteration of the pulmonary parenchyma, with changes in the connective tissue, obliteration of the alveoli and dilatation of the air spaces, which is known as honeycombing. Continuous lung injury and repair result in restrictive lung disease, the increased work of breathing and a functionally reduced lung volume, thus leading to an impaired gas exchange. The chest X-ray may be within normal limits, but it can show a pattern of diffuse interstitial markings. The pulmonary function tests can show a restrictive pattern when pulmonary fibrosis has occurred before the clinical symptoms have appeared.
But few studies have been carried out, which do not show similar results. Ooi et al (8)(2001) found lung function indices including FVC,FEV1,TLC and DLCO, in patients who received chemotherapy, but did not have significant declined lung function indices. According to Dimopoulou et al (9) (2002), after chemotherapy, there were no significant changes in the forced vital capacity (FVC), FEV1,TLC or the alveolar volume.
The present study highlights the observation that most of the spirometric parameters in cancer patients after chemotherapy showed a significant decline. Some drugs may cause direct damage to the lung parenchyma, like Bleomycin, Cyclophosphamide and Nitrofurantoin which can cause the generation of toxic oxygen free radicals. Others may act on the system, whereby the lung matrix repairs itself, interfering with or increasing collagen formation. In some cases, this restrictive type of abnormality is associated with an obstructive pattern as well. In case of intrinsic drug induced lung diseases, the physiological effects of the diffuse parenchymal disorder reduce all the lung volumes, probably by the excessive elastic recoil of the lungs in comparison to the outward recoil of the chestwall. The expiratory airflow is reduced in proportion to the lung volumes. This decline after chemotherapy is probably due to the toxicity of the various chemotherapeutic drugs.
- Emerging Sources Citation Index (Web of Science, thomsonreuters)
- Index Copernicus ICV 2017: 134.54
- Academic Search Complete Database
- Directory of Open Access Journals (DOAJ)
- Google Scholar
- HINARI Access to Research in Health Programme
- Indian Science Abstracts (ISA)
- Journal seek Database
- Popline (reproductive health literature)