Increased exhaled nitric oxide following autologous peripheral hematopoietic stem-cell transplantation: a potential marker of idiopathic pneumonia syndrome

BACKGROUND: Increased production of nitric oxide (NO) and oxidative stress following bone marrow transplantation may play a role in the pathogenesis of idiopathic pneumonia syndrome (IPS). We hypothesize that patients who received high-dose chemotherapy followed by autologous peripheral hematopoietic stem-cell transplantation (APHSCT) have increased exhaled NO. METHOD: We measured exhaled lower respiratory tract NO concentration with a chemiluminescent NO analyzer during a slow vital capacity maneuver against a positive pressure of 16 cm H(2)O at an expiratory flow rate of 50 mL/s in 20 female patients who received high-dose chemotherapy (cyclophosphamide, carmustine, and cisplatin) followed by APHSCT for the treatment of stage III or IV breast carcinoma. Pulmonary function tests were performed, and exhaled NO measurements and clinical and laboratory data were obtained before transplantation and at every 6-week visit after transplantation for 24 weeks. RESULTS: All study patients had evidence of IPS with dyspnea and reduction in diffusion capacity of the lung for carbon monoxide (DLCO). Lower respiratory tract exhaled NO was significantly higher after APHSCT and during the 6 months of follow-up. Mean (+/- SD) exhaled NO increased from (mean +/- SD) 12.54 +/- 1.32 parts per billion (ppb) before APHSCT to 21.26 +/- 1.94 ppb at 6 weeks (p = 0.099), 21.26 +/- 1.94 ppb (p = 0.006) at 12 weeks, 24.62 +/- 2.55 ppb (p = 0.012) at 18 weeks, and 25.28 +/- 3.31 ppb (p = 0.013) at 24 weeks (all p values were compared to baseline). There was a strong negative correlation between DLCO and exhaled NO (regression coefficient - 0.60, p = 0.01). CONCLUSION: Lower respiratory tract concentration of exhaled NO is significantly increased following APHSCT and correlates with reduction in DLCO. Increase in lower respiratory tract concentration of NO is a potential marker of IPS.     

Pulmonary function 4 months after coronary artery bypass graft surgery

The objective of this study was to describe the pulmonary function and pain 4 months after coronary artery bypass graft surgery. Twenty-five male patients performed pulmonary function tests before surgery, on the 4th postoperative day and 4 months after surgery. A severe reduction in pulmonary function was present after surgery. Four months postoperatively, the patients still showed a significant decrease (6-13% of preoperative values) in vital capacity (P<0.001), inspiratory capacity (P<0.001), forced expiratory volume in 1 s (P<0.001) peak expiratory flow rate (P<0.001), functional residual capacity (P=0.05) total lung capacity (P<0.001) and single-breath carbon monoxide diffusing capacity (P<0.01). Residual volume and single-breath carbon monoxide diffusing capacity per litre of alveolar volume had returned to the preoperative level. Four months postoperatively, the median values for sternotomy pain while taking a deep breath was 0.2 and while coughing 0.3 on a 10 cm visual analogue pain scale. In conclusion, a significant restrictive pulmonary impairment persisting up to 4 months into the postoperative period was found after CABG. Measured levels of pain were low and could not explain the impairment.     

Increased circulating levels of alpha1-antitrypsin and calprotectin are associated with reduced gas diffusion in the lungs.

The aim was to examine the relationship of serum inflammatory markers to the level of single-breath diffusing capacity of carbon monoxide (TL,CO). A stratified sample (n = 1,121) of a Norwegian general population aged 18-73 yrs was examined. The inflammatory markers measured were calprotectin, a prominent protein in the cytosol fraction of neutrophil granulocytes, and alpha1-antitrypsin (alpha1-AT), the major inhibitor of neutrophil elastase in the lower respiratory system. Both markers have increased circulating levels in the course of an acute inflammatory reaction. Subjects with a TL,CO < 80% of predicted value had a higher level of both alpha1-AT (p = 0.003) and calprotectin (p < 0.03) than those with a TL,CO > 100%. In multiple linear regression analyses, alpha1-AT was still significantly associated with TL,CO after adjusting for sex, age, smoking habits, haemoglobin, carboxyhaemoglobin, forced expiratory volume in one second and alveolar volume. In a similar analysis, no significant overall association was found between calprotectin and TL,CO, but in a stratified analysis, calprotectin was significantly related to TL,CO in females. However, no significant sex interaction in the relationship between the inflammatory markers and TL,COo was found. The findings suggest that increased levels of alpha1-antitrypsin and of calprotectin are risk factors for decreased diffusing capacity of carbon monoxide.     

Role of diffusing capacity in predicting complications after lung resection for cancer

BACKGROUND: The purpose of our study was to determine whether the assessment of the diffusing capacity of the lung for carbon monoxide (DL (CO)), together with the forced expiratory volume in 1 second (FEV (1)), could improve the selection of surgical patients. METHODS: The data of 76 patients undergoing major lung resection (pnemonectomy, bilobectomy or lobectomy) for non-small cell lung cancer were retrospectively studied. All patients were reviewed for age, sex, preexisting medical conditions, operative, and pathological findings and postoperative outcome. RESULTS: Univariate and multivariable logistic regression analysis showed that ppoFEV (1) and ppoDL (CO) were the only statistically significant predictors of pulmonary complications. In the group of patients with marginal ppoFEV (1) (between 30 - 40 %), ppoDL (CO) predicted pulmonary morbidity with a better accuracy ( P < 0.005) than ppoFEV (1) ( P > 0.05). Multiple regression analysis showed that pneumonectomy was the only statistical factor correlated with mortality ( P < 0.05). CONCLUSION: Our experience seems to suggest that ppoDL (CO) is a strong predictor of pulmonary complications after major lung resection, allowing a better surgical selection of the patients with compromised respiratory function.     

Acute and chronic pulmonary function changes in allergic bronchopulmonary aspergillosis.

Pulmonary functions of patients with allergic bronchopulmonary aspergillosis were studied during an acute episode (n = 6); during a mean follow-up period of 44 months (range four months--14.8 years) (n = 16); and for any correlation between duration of ABPA and asthma with the total lung capacity (helium dilution), 1 second forced expiratory volume (FEV1), vital capacity, 1 second forced expiratory volume-forced vital capacity ratio (FEV1:FVC per cent) and diffusing capacity of carbon monoxide (DL:CO) (single breath) for the entire group (n = 22). All patients were treated with corticosteroids (intermittent or continuous) and bronchodilators. For the 16 patients, slopes using linear regression analysis were determined from the function as per cent predicted versus time in months from diagnosis and then analyzed for significance. Significant functional loss was shown in three of 16 patients for FEV1, two of 16 patients for vital capacity, one of 16 patients for FEV1:FVC per cent, none of 10 patients for DL:CO and one of 10 patients for total lung cital capacity, FEV1:FVC per cent and the duration of asthma or allergic bronchopulmonary aspergillosis was found by multiple regression analysis correcting for age and smoking (mean 4.24 years; range 0.3 to 14.8 years). Roentgenographic criteria and blood eosinophilia were used to define a "flare" of allergic bronchopulmonary aspergillosis. The six patients during a flare showed a significant reduction in total lung capacity (P less than 0.001), vital capacity (P less than 0.05), FEV1 (P less than 0.01) and DL:CO (P less than 0.001) which uniformly returned to baseline values during steroid therapy. The FEV1:FVC per cent remained unaltered. These findings, contrary to suggestions in the literature, indicate that in the majority of our patients there was no significant progressive functional deterioration after diagnosis. However, during acute episodes of allergic bronchopulmonary aspergillosis, transient reduction of volumes and DL:CO were uniformly present.     

Preoperative and postoperative pulmonary function tests in patients with atrial septal defect and their relation to pulmonary artery pressure and pulmonary:systemic flow ratio

Pulmonary diffusing properties and lung volumes were investigated in 44 patients with atrial septal defect, and in 30 of them preoperative and postoperative data were obtained. The patients were divided into three groups according to mean pulmonary artery pressure: less than or equal to 15 mm Hg (group 1), 16-29 mm Hg (group 2), and greater than or equal to 30 mm Hg (group 3). Patients in groups 1 and 2 had a high carbon monoxide transfer test which became normal after surgical correction of their septal defect. In group 3, the carbon monoxide transfer test was normal both before and after operation. As mean pulmonary artery pressure increased there was a progressive reduction in both forced expiratory volume in one second and vital capacity. Patients in group 3 had a low forced expiratory volume in one second, a low vital capacity, and a reduced forced expiratory volume in one second:vital capacity ratio. These abnormalities were not corrected by surgical closure of the septal defect. Formulas were derived from the lung function data, to predict the mean pulmonary artery pressure and the pulmonary:systemic flow ratio. The values predicted when these two formulas were applied to data obtained for patients in this study correlated well with measured values.     

Effect of pattern and severity of respiratory muscle weakness on carbon monoxide gas transfer and lung volumes.

In clinical practice, an elevated carbon monoxide (CO) transfer coefficient (KCO) and restrictive ventilatory defect are taken as features of respiratory muscle weakness (RMW). However, the authors hypothesised that both pattern and severity of RMW effect gas transfer and lung volumes. Measurements of CO transfer and lung volumes were performed in patients with isolated diaphragm weakness (n=10), inspiratory muscle weakness (n=12), combined inspiratory and expiratory muscle weakness (n=5) and healthy controls (n=6). Patients with diaphragm weakness and inspiratory muscle weakness had reduced total lung capacity (TLC) (83.6% predicted and 68.9% pred, respectively), functional residual capacity (FRC) (83.9% pred and 83.6% pred) and transfer factor of the lung for CO (TL,CO) (86.2% pred and 66.2% pred) with increased KCO (114.1% pred and 130.2% pred). Patients with combined inspiratory and expiratory muscle weakness had reduced TLC (80.9% pred) but increased FRC (109.9% pred) and RV (157.4% pred) with decreased TL,CO (58.0% pred) and KCO (85.5% pred). In patients with diaphragm weakness, the increase in carbon monoxide transfer coefficient was similar to that of normal subjects when alveolar volume was reduced. However, the increase in carbon monoxide transfer coefficient in inspiratory muscle weakness was often less than expected, while in combined inspiratory and expiratory muscle weakness, the carbon monoxide transfer coefficient was normal/reduced despite further reductions in alveolar volume, which may indicate subtle abnormalities of the lung parenchyma or pulmonary vasculature. Thus, this study demonstrates the limitations of using carbon monoxide transfer coefficient in the diagnosis of respiratory muscle weakness, particularly if no account is taken of the alveolar volume at which the carbon monoxide transfer coefficient is made.     

Preoperative and postoperative pulmonary function tests in patients with atrial septal defect and their relation to pulmonary artery pressure and pulmonary:systemic flow ratio.

Pulmonary diffusing properties and lung volumes were investigated in 44 patients with atrial septal defect, and in 30 of them preoperative and postoperative data were obtained. The patients were divided into three groups according to mean pulmonary artery pressure: less than or equal to 15 mm Hg (group 1), 16-29 mm Hg (group 2), and greater than or equal to 30 mm Hg (group 3). Patients in groups 1 and 2 had a high carbon monoxide transfer test which became normal after surgical correction of their septal defect. In group 3, the carbon monoxide transfer test was normal both before and after operation. As mean pulmonary artery pressure increased there was a progressive reduction in both forced expiratory volume in one second and vital capacity. Patients in group 3 had a low forced expiratory volume in one second, a low vital capacity, and a reduced forced expiratory volume in one second:vital capacity ratio. These abnormalities were not corrected by surgical closure of the septal defect. Formulas were derived from the lung function data, to predict the mean pulmonary artery pressure and the pulmonary:systemic flow ratio. The values predicted when these two formulas were applied to data obtained for patients in this study correlated well with measured values.     

Intensive radio-chemotherapy with peripheral blood stem cell transplantation in young patients with chronic lymphocytic leukemia.

Two patients with previously treated CLL received autologous PBSC transplantation after total body irradiation and high-dose chemotherapy. Before intensification, a partial marrow response had been obtained in both patients, with disappearance of peripheral blood involvement as shown by immunophenotypic assessment using fludarabine. PBSC collection was performed after a single course of high-dose cyclophosphamide followed by GM-CSF administration. One patient failed to reconstitute normal hematopoiesis and died 3 months post-transplant. The other is in continuous complete remission 12 months after intensification. This strategy in young patients with poor prognosis CLL warrants further investigation.     

Decrease in lung recoil pressure after cessation of smoking.

Tests of lung mechanics and single-breath carbon monoxide diffusing capacity (DLCO) were done in 26 apparently healthy cigarette smokers before and 2 months after cessation of smoking. There was a significant increase in vital capacity and 1-sec forced expiratory volume as well as improvement in frequency dependence of lung dynamic compliance. Slope and phase III and density dependence of maximal expiratory flow showed a borderline improvement DLCO did not change. Static lung pressure-volume curves showed a small but significant (P less than 0.01) shift toward lower pressures. We concluded that the previously reported decrease in lung recoil pressure observed in smokers is even more accentuated after cessation of smoking.     

Treatment of Idiopathic Pulmonary Fibrosis with Losartan: A Pilot Project

Background

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease with no current effective therapies. Treatment has focused on antifibrotic agents to stop proliferation of fibroblasts and collagen deposition in the lung. We present the first clinical trial data on the use of losartan, an antifibrotic agent, to treat idiopathic pulmonary fibrosis. The primary objective was to evaluate the effect of losartan on progression of idiopathic pulmonary fibrosis measured by the change in percentage of predicted forced vital capacity (%FVC) after 12?months. Secondary outcomes included the change in forced expiratory volume at 1 second, diffusing capacity of carbon monoxide, 6-minute walk test distance, and baseline/transition dyspnea index.

Methods

Patients with idiopathic pulmonary fibrosis and a baseline %FVC of ≥50?% were treated with losartan 50?mg by mouth daily for 12?months. Pulmonary function testing, 6-minute walk, and breathlessness indices were measured every 3?months.

Results

Twenty participants with idiopathic pulmonary fibrosis were enrolled and 17 patients were evaluable for response. Twelve patients had a stable or improved %FVC at study month 12. Similar findings were observed in secondary end-point measures, including 58, 71, and 65?% of patients with stable or improved forced expiratory volume at 1 second, diffusing capacity for carbon monoxide, and 6-minute walk test distance, respectively. No treatment-related adverse events that resulted in early study discontinuation were reported.

Conclusion

Losartan stabilized lung function in patients with idiopathic pulmonary fibrosis over 12?months. Losartan is a promising agent for the treatment of idiopathic pulmonary fibrosis and has a low toxicity profile.     

High-dose chemotherapy and autologous hematopoieticstem cell transplantation in patients with second primary malignancies

We treated 500 patients with high-dose chemotherapy and autologous bone marrow or autologous peripheral blood stem cell transplantation. Treated conditions included leukemia, lymphoma, breast cancer, lung cancer, germ-cell carcinoma, and other solid tumors. 10/500 (2%) of patients were treated for a second malignancy diagnosed 12 months to 25 years after their initial neoplasm. Four of these ten patients are in complete remission (CR) of both malignancies at a median follow-up of 29+ months after high-dose chemotherapy and autotransplantation. None of these patients would have been eligible for high-dose chemotherapy and autotransplantation by conventional selection criteria which usually exclude patients with a history of prior malignancies. Conclusion. Conventional exclusion criteria for high-dose chemotherapy and autotransplantation may not adequately reflect the prognosis of patients with second or secondary malignancies treated with this therapeutic modality. High-dose chemotherapy and autologous hematopoietic stem cell transplantation may be of true benfit in selected cases of secondary malignancies.     

Effects on diffusing capacity and ventilation--perfusion relationships of budesonide inhalations for 2 months in chronic obstructive pulmonary disease (COPD).

Forced expiratory volumes are reduced in chronic obstructive pulmonary disease (COPD), mainly as a result of inflammatory and morphological changes in the small airways (with a diameter < 2 mm) and in the alveoli. However, it is difficult to detect minor changes in small airways by spirometry measurements. To study the effects on small airways of inhaled corticosteroids (ICS), 19 stable COPD patients were investigated; 15 were evaluated by ventilation-perfusion (V(A)/Q) relationships, assessed by the multiple inert gas elimination technique, and by diffusing capacity for carbon monoxide (DL(CO)), assessed by the single breath technique. Measurements were repeated after 2 months of budesonide inhalations (800 microg) twice daily. Before ICS treatment: mean forced expiratory volume in 1 sec (FEV1) as a percentage of predicted (% P) was 40.1 (+/- 16.0)%, DL(CO)% P was 45.7 (+/- 25.0)% and 6.0 (+/- 6.4)% of the ventilation was directed at high V(A)/Q areas. The mean of the V(A)/Q ratio for ventilation (V-mean) was 2.7 times higher than normal. After 2 months of ICS: the mean of DL(CO)% P increased by 8.6 (+/- 19.4)%, and FEV1/vital capacity decreased by 6.9 (+/- 11.3)%. Basal morning and ACTH-stimulated S-cortisol levels were significantly reduced. All the V(A)/Q relationships remained unchanged. In conclusion, a significant increase in diffusion capacity for carbon monoxide levels after treatment with corticosteroid inhalations for 2 months was shown, but no significant improvements were found in forced expiratory airflow, lung volumes, or V(A)/Q relationships.     

The alveolar-capillary membrane diffusing capacity and the pulmonary capillary blood volume in heart transplant candidates

OBJECTIVES: To determine the mechanism of impairment of pulmonary transfer factor for carbon monoxide (TL(CO)) in heart transplant candidates, as this is the most common lung function abnormality. SETTING: Regional cardiopulmonary transplant centre. METHODS: TL(CO) and its components (the diffusing capacity of the alveolar-capillary membrane (D(M)) and the pulmonary capillary blood volume (V(C))) were measured using the Roughton and Forster method and the single breath technique in 38 patients with severe chronic heart failure awaiting heart transplantation (mean age 51 years, range 19 to 61; mean left ventricular ejection fraction 12.8%). Results were compared with data from 26 normal subjects (mean age 47 years, range 27 to 62). RESULTS: Mean per cent predicted TL(CO), D(M), and V(C) were significantly reduced in patients (69.9%, 81.4%, and 80.2% of predicted, respectively) compared with controls (97.7%, 100.1%, and 102.3% of predicted, respectively, p < 0.001). The relative contribution of the two components of TL(CO) in patients was similar to that of normal subjects, with each component accounting for approximately 50% of the total resistance to diffusion (1/TL(CO)). CONCLUSIONS: TL(CO) impairment in patients with severe chronic heart failure awaiting heart transplantation results from a proportionate reduction in both D(M) and V(C), suggesting a significant disturbance of the pulmonary vascular bed.     

Autologous peripheral blood stem cell transplantation for peripheral neuropathy secondary to monoclonal gammopathy of unknown significance

A 40-year-old patient presented with rapidly progressing peripheral neuropathy secondary to monoclonal gammopathy of unknown significance (MGUS). He became severely debilitated, being wheelchair-bound, despite treatment with chemotherapy, intravenous immunoglobulin and plasma exchange. He was subsequently treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT). He has made remarkable recovery at 12 months post transplantation. We propose that high-dose chemotherapy and autologous PBSC transplantation may have a role in the treatment of severe, progressive and treatment-resistant MGUS-related peripheral neuropathy.     

Consolidation therapy with autologous blood stem cell transplantation in a patient with primary plasma cell leukaemia

Primary plasma cell leukaemia (PPCL) is a rare form of plasma cell dyscrasia. Conventional melphalan-based treatment is often ineffective, with a reported median survival of 2-7 months only. We report a 53-year-old man with PPCL who was treated with four cycles of combination chemotherapy including vincristine, adriamycin and dexamethasone that resulted in a good partial remission. High-dose melphalan 200 mg/m2 and autologous peripheral blood stem cell (PBSC) rescue was then given 6 months after diagnosis. Maintenance interferon-alpha was started 8 weeks after transplantation with good drug compliance. Complete remission was achieved and molecular remission was documented 11 months after autologous PBSC transplantation. In conclusion, high-dose therapy followed by autologous stem cell rescue is a feasible option for PPCL that can result in a reasonably sustained remission.     

Airflow limitation in morbidly obese, nonsmoking men

STUDY OBJECTIVE: To determine the effect of obesity on pulmonary function. DESIGN: Case-control study, using nonobese, age- and height-matched [corrected] nonsmokers. SETTING: Metabolic and obesity clinics of two major teaching hospitals. PATIENTS: One hundred and three obese, lifelong nonsmokers without cardiopulmonary disease. CONTROLS: One hundred and ninety healthy, nonobese nonsmokers recruited from among hospital personnel. MEASUREMENTS AND MAIN RESULTS: Complete pulmonary function measurements in all patients and controls. These measurements included maximum expiratory flow-volume curve, lung volumes and airway resistance using body plethysmograph, single-breath diffusing capacity for carbon monoxide, and total lung capacity using the helium dilution technique. Obese persons were found to have lower functional residual capacity, expiratory reserve volume, and total lung capacity by helium dilution than nonobese controls. In addition, residual volume and diffusing capacity were higher in the obese group. Finally, we found that obese men, but not women, had reduced maximum expiratory flow rates at 50% and 75% of exhaled vital capacity. CONCLUSION: Obesity may contribute independently of smoking habits to chronic airflow limitation in men.     

Longitudinal changes of body mass index, spirometry and diffusion in a general population.

The aim of this study was to evaluate the effects of body mass index (BMI) changes over an 8-yr follow-up, on longitudinal changes of vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and carbon monoxide diffusing capacity of the lung (DL,CO) indices in a general population sample of North Italy. To avoid including weight changes possibly related to physical growth, only the 1,426 adults (>24 yrs, 46% males) with complete follow-up were selected. Median linear regression models were applied to estimate the medians of change (computed as follow-up minus baseline values) of VC, FVC, FEV1 and DL,CO indices, as functions of changes of BMI over the follow-up period, separately by sex, after considering several potential confounders and effect modifiers. The extent of lung function loss tended to be higher among those who, at baseline, reported greater BMI values. Males experienced larger losses than females (20 and 16 mL FEV1 median reduction for a BMI unit increase in males and females, respectively). Conversely, longitudinal changes of BMI caused a slight and nonsignificant increase in DL,CO values in both sexes. Over an 8-yr follow-up, the detrimental effect of gaining weight might be reversible for many adults as most of those who reduced their body mass index values also increased their lung function. Overweight patients with ventilatory impairment should be routinely encouraged to lose weight for improving their lung function.     

Respiratory function in children undergoing bone marrow transplantation.

We conducted a prospective study of respiratory function in children undergoing bone marrow transplantation (BMT) for onco-hematological disorders. Each child was evaluated before and 100 days after BMT. The investigations included clinical examination, chest X-ray, and pulmonary function tests (PFT) to determine: slow vital capacity (VC), functional residual capacity (FRC), total lung capacity (TLC), forced expiratory volume in 1 s (FEV1), carbon monoxide diffusing capacity (DLCO), ratio of residual volume (RV) to TLC, and FEV1/VC. The values obtained before and after BMT were compared to predicted values, and the post-BMT values were compared to the pre-BMT values (Student's t-test). From 1986 to 1995, 77 children underwent BMT, of whom 39 were available for testing. The pre-BMT VC (P = 0.0234) and DLCO (P < 0.0001) were lower and FRC higher (P < 0.0001) than predicted values. After BMT, the VC (P = 0.004), TLC (P = 0.044), and FEV1 (P = 0.012) were lower, and the RV/TLC ratio was higher (P = 0.043), compared with pre-BMT data. The observed respiratory abnormalities were not clinically relevant. The only identifiable risk factor for a decrease in lung function was age at BMT. This study shows that some lung dysfunction may be present before BMT and be further altered by BMT. This stresses the need for longitudinal respiratory monitoring and follow up to detect such dysfunctions and to insure an optimal treatment program for these children.     

Energy metabolism, respiratory heat loss, and lung functions in patients with chronic obstructive pulmonary disease and pulmonary fibrosis]

Resting energy expenditure (REE) and respiratory heat loss (RHL) were measured in 17 patients with chronic obstructive pulmonary disease (COPD), 7 patients with pulmonary fibrosis (PF), and 8 normal healthy subjects, three hours after a light breakfast. Correlations between these values, and also predicted basal metabolic rate (PreBMR) and normalized lung functions were assessed. REE, REE/Pre BMR, RHL and RHL/REE in all patients increased significantly compared with those of control subjects. When all the studied subjects were combined, significant negative relationships were found between REE, REE/PreBMR, RHL and RHL/REE and percent predicted values of forced expiratory volume in one second (FEV1.0), between RHL and RHL/REE and percent predicted values of vital capacity (VC), and between REE/PreBMR, RHL and RHL/REE and percent predicted values of carbon monoxide diffusing capacity (DLCO). These results indicate that resting energy expenditure and respiratory heat loss increase in patients with COPD and PF in association with even slight to moderate deterioration of lung function. Therefore, elevated resting energy expenditure and respiratory heat loss need to be taken into account in determining caloric and water requirements of these patients.