Search tips
Search criteria

Results 1-25 (1203404)

Clipboard (0)

Related Articles

1.  Systemic and Discoid Lupus Erythematosus: Analysis of Pulmonary Function 
To determine the prevalence of pulmonary dysfunction in lupus erythematosus, 24 patients with systemic lupus erythematosus (SLE) and 5 patients with discoid lupus erythematosus (DLE) were studied. Diffusing capacity for carbon monoxide was abnormal in 17 (71 percent) SLE patients. A restrictive ventilatory defect was present in 6 (25 percent) and arterial hypoxemia in 4 of 23 (17 percent). The mean ratio of forced expiratory volume in one second to forced vital capacity (FVC) was 83 percent. To test for the presence of small airways disease, maximum expiratory flow rate at 50 percent of FVC was measured on air and on an 80 percent helium-20 percent oxygen mixture. Ten patients (5 smokers and 5 nonsmokers) with SLE were nonresponders to helium suggesting small airways disease. Pulmonary dysfunction was present in 90 percent (9/10) of SLE patients with a previous history of pleuritis and/or pneumonitis, and in 71 percent (10/14) without respiratory symptoms or history of lung disease and with a normal chest radiograph. Pulmonary function tests were normal in DLE patients except for an abnormal response to helium and/or mild arterial hypoxemia in two patients, all of whom were smokers. These data indicate that there is a high prevalence of pulmonary function abnormalities in SLE including patients without clinically evident pleuropulmonary disease.
PMCID: PMC2595677  PMID: 685297
2.  Respiratory disease in systemic lupus erythematosus: correlation with results of laboratory tests and histological appearance of muscle biopsy specimens. 
Thorax  1992;47(11):957-960.
BACKGROUND: In systemic lupus erythematosus, certain laboratory tests and evidence from muscle biopsy specimens of lymphocytic vasculitis reflect disease activity. A study was designed to determine if such indices predict respiratory lesions, and in particular whether the presence of vasculitis in quadriceps muscle reflects respiratory muscle function. METHODS: Twenty seven 27 patients with systemic lupus erythematosus were studied, ten of whom were consecutive untreated patients and 17 having clinically active disease and being treated. They were prospectively evaluated on the basis of erythrocyte sedimentation rate, lymphocyte count, C3 degradation products, quadriceps muscle biopsy, spirometry, lung volumes, carbon monoxide transfer factor, and mouth pressure during a maximal sniff. RESULTS: Lung function test results were abnormal in 12 patients. Vital capacity was reduced in seven, carbon monoxide transfer factor capacity in five, and mouth pressure was low (< 70% predicted) in ten. Lymphocytic vasculitis was seen in the muscle biopsy specimens of ten patients. No correlation was found between laboratory tests and lung function or mouth pressure, or between the presence of lymphocytic vasculitis and mouth pressure. In untreated patients, those with lymphocytic vasculitis had lower spirometric values. CONCLUSIONS: In systemic lupus erythematosus, evidence from muscle biopsy specimens of lymphocytic vasculitis is not predictive of impaired inspiratory muscle function as measured by mouth pressure. In untreated patients there were relationships between some laboratory test results and respiratory function, but this was not the case for the whole group. In systemic lupus erythematosus, laboratory tests and evidence from muscle biopsy specimens of lymphocytic vasculitis are therefore unlikely to be helpful in the assessment of respiratory disease.
PMCID: PMC464109  PMID: 1465755
3.  Pulmonary involvement in systemic lupus erythematosus. 
Annals of the Rheumatic Diseases  1978;37(6):536-539.
Several series have suggested that pulmonary function abnormalities are common in systemic lupus erythematosus. However, only isolated studies have attempted to relate these abnormalities to immunological aspects of the diseases. In the present study respiratory symptoms, pulmonary function tests, and immunological data were reviewed in 22 patients with systemic lupus erythematosus. Seventeen subjects had either clinical evidence or abnormalities of lung function suggestive of pulmonary involvement. A restrictive ventilatory defect or reduction in pulmonary diffusing capacity for carbon monoxide was demonstrated in 14 of the patients only 4 of whom were dyspnoeic. There was no correlation between pulmonary involvement, co-existent renal lupus, and immunological abnormality.
PMCID: PMC1000291  PMID: 749699
4.  MMP1 and MMP7 as Potential Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis 
PLoS Medicine  2008;5(4):e93.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease associated with substantial morbidity and mortality. The objective of this study was to determine whether there is a peripheral blood protein signature in IPF and whether components of this signature may serve as biomarkers for disease presence and progression.
Methods and Findings
We analyzed the concentrations of 49 proteins in the plasma of 74 patients with IPF and in the plasma of 53 control individuals. We identified a combinatorial signature of five proteins—MMP7, MMP1, MMP8, IGFBP1, and TNFRSF1A—that was sufficient to distinguish patients from controls with a sensitivity of 98.6% (95% confidence interval [CI] 92.7%–100%) and specificity of 98.1% (95% CI 89.9%–100%). Increases in MMP1 and MMP7 were also observed in lung tissue and bronchoalveolar lavage fluid obtained from IPF patients. MMP7 and MMP1 plasma concentrations were not increased in patients with chronic obstructive pulmonary disease or sarcoidosis and distinguished IPF compared to subacute/chronic hypersensitivity pneumonitis, a disease that may mimic IPF, with a sensitivity of 96.3% (95% CI 81.0%–100%) and specificity of 87.2% (95% CI 72.6%–95.7%). We verified our results in an independent validation cohort composed of patients with IPF, familial pulmonary fibrosis, subclinical interstitial lung disease (ILD), as well as with control individuals. MMP7 and MMP1 concentrations were significantly higher in IPF patients compared to controls in this cohort. Furthermore, MMP7 concentrations were elevated in patients with subclinical ILD and negatively correlated with percent predicted forced vital capacity (FVC%) and percent predicted carbon monoxide diffusing capacity (DLCO%).
Our experiments provide the first evidence for a peripheral blood protein signature in IPF to our knowledge. The two main components of this signature, MMP7 and MMP1, are overexpressed in the lung microenvironment and distinguish IPF from other chronic lung diseases. Additionally, increased MMP7 concentration may be indicative of asymptomatic ILD and reflect disease progression.
Naftali Kaminski and colleagues find increased levels of specific proteins in the bloodstream of individuals with idiopathic pulmonary fibrosis, and suggest that these proteins may ultimately provide a biomarker for the disease.
Editors' Summary
Idiopathic pulmonary fibrosis (IPF) is a serious disease in which the lungs become progressively scarred or thickened for unknown reasons. In healthy people, air is taken in through the mouth or nose and travels down the windpipe into tubes in the lungs called the airways. Each airway has many small branches that end in alveoli, tiny air sacs with thin walls that are surrounded by small blood vessels called capillaries. When air reaches the alveoli, the oxygen in it passes into the bloodstream and is taken to the organs of the body to keep them working. In IPF, the alveoli and the space around them (the “interstitial” area) gradually become scarred and thickened, which stops oxygen's movement into the bloodstream. When only small areas of the lung are scarred, IPF may cause no symptoms. But, as more of the lung becomes damaged, IPF eventually causes breathlessness, even when resting. There is no effective treatment for IPF, although steroids and drugs that suppress the body's immune system are often tried in an attempt to slow its progression. On average, half of the people with IPF die within three years of diagnosis, often from respiratory or heart failure.
Why Was This Study Done?
It can be difficult to diagnose IPF—there are many lung diseases with similar symptoms, including numerous other interstitial lung diseases—and currently, physicians can only follow the progression of IPF by repeatedly testing their patients' lung function or by doing multiple chest X-rays. If proteins could be identified whose level in blood indicated disease activity (so-called “peripheral blood biomarkers”), it would be easier to diagnose and monitor patients. In addition, the identification of such biomarkers might suggest new drug targets for the treatment of IPF. In this study, the researchers look for peripheral blood biomarkers in IPF by using a “multiplex analysis” system to measure the level of several proteins in patient blood samples simultaneously.
What Did the Researchers Do and Find?
The researchers measured the levels of 49 plasma proteins (plasma is the fluid part of blood) in 74 patients with IPF and 53 healthy people (controls) and used a technique called “recursive partitioning” to define a five-protein signature that distinguished patients from unaffected study participants (controls). Matrix metalloproteinase 7 (MMP7) and MMP1—the two plasma proteins whose levels were most increased in patients with IPF compared to controls—were key components of this signature. Concentrations of MMP7 and MMP1 were higher in bronchoalveolar lavage samples (fluid obtained by washing out the lungs with saline) and in lung tissue samples from patients with IPF than in similar samples taken from healthy individuals. Plasma concentrations of MMP7 and MMP1 were significantly higher in patients with IPF than in patients with hypersensitivity pneumonitis, an interstitial lung disease that mimics IPF, but not increased in patients with chronic obstructive pulmonary disease or sarcoidosis, two other lung diseases. In an independent validation group, patients with IPF and familial pulmonary fibrosis had increased plasma concentrations of MMP7 and MMP1 that correlated with the severity of their disease. In addition, MMP7 concentrations were raised in close relatives of people with familial pulmonary fibrosis who had normal lung function tests but some lung scarring.
What Do These Findings Mean?
These findings provide evidence for a protein signature in the blood for IPF and suggest MMP1 and MMP7 may be useful as biomarkers for IPF. These two matrix metalloproteinases have previously been suggested to be involved in the development of IPF. However, additional work is probably needed to confirm that increased plasma concentrations MMP7 and MMP1 are specific for IPF, since it may be that these markers will not distinguish IPF from other interstitial lung diseases.
Additional Information.
Please access these Web sites via the online version of this summary at
Read a related PLoS Medicine Perspective article
The MedlinePlus Encyclopedia has a page on idiopathic pulmonary fibrosis (in English and Spanish) and on pulmonary fibrosis
The US National Heart Lung and Blood Institute and the British Lung Foundation also provide information on IPF for patients and relatives
Some of the researchers involved in this study provide more details about what might go wrong in IPF in a recent PLoS Medicine article
PMCID: PMC2346504  PMID: 18447576
5.  Age-related changes in Serum Growth Hormone, Insulin-like Growth Factor-1 and Somatostatin in System Lupus Erythematosus 
Systemic lupus erythematosus is an age- and gender-associated autoimmune disorder. Previous studies suggested that defects in the hypothalamic/pituitary axis contributed to systemic lupus erythematosus disease progression which could also involve growth hormone, insulin-like growth factor-1 and somatostatin function. This study was designed to compare basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels in female systemic lupus erythematosus patients to a group of normal female subjects.
Basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels were measured by standard radioimmunoassay.
Serum growth hormone levels failed to correlate with age (r2 = 3.03) in the entire group of normal subjects (i.e. 20 – 80 years). In contrast, serum insulin-like growth factor-1 levels were inversely correlated with age (adjusted r2 = 0.092). Of note, serum growth hormone was positively correlated with age (adjusted r2 = 0.269) in the 20 – 46 year range which overlapped with the age range of patients in the systemic lupus erythematosus group. In that regard, serum growth hormone levels were not significantly higher compared to either the entire group of normal subjects (20 – 80 yrs) or to normal subjects age-matched to the systemic lupus erythematosus patients. Serum insulin-like growth factor-1 levels were significantly elevated (p < 0.001) in systemic lupus erythematosus patients, but only when compared to the entire group of normal subjects. Serum somatostatin levels differed from normal subjects only in older (i.e. >55 yrs) systemic lupus erythematosus patients.
These results indicated that systemic lupus erythematosus was not characterized by a modulation of the growth hormone/insulin-like growth factor-1 paracrine axis when serum samples from systemic lupus erythematosus patients were compared to age- matched normal female subjects. These results in systemic lupus erythematosus differ from those previously reported in other musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis, fibromyalgia, diffuse idiopathic skeletal hyperostosis and hypermobility syndrome where significantly higher serum growth hormone levels were found. Somatostatin levels in elderly systemic lupus erythematosus patients may provide a clinical marker of disease activity in these patients.
PMCID: PMC529450  PMID: 15496230
6.  Pulmonary function testing and chest tomography in patients with acromegaly 
Despite the gradual improvement in treatment procedures and cure rates of acromegaly, a steady increase in the mortality rate due to respiratory disease has been documented in recent decades. In this study, our objectives were to describe the abnormalities in lung structure and function that occur in acromegalic patients and to correlate these changes with hormonal levels.
This cross-sectional study included 20 acromegalic patients and 20 age-and height-matched control subjects, all non-smokers. All subjects underwent spirometry, whole body plethysmography, carbon monoxide diffusing capacity, and respiratory muscle strength. Acromegalic patients also performed high-resolution computed tomography (HRCT).
Most patients were female (65%), with a mean age of 52.5 ± 13 years. Acromegalic patients showed lower values of maximum expiratory pressure (55.9 ± 17.1 vs. 103.7 ± 19.2%; p < 0.001) and maximum inspiratory pressure (71.4 ± 27.8 vs. 85.3 ± 24.1%; p = 0.005) compared to control subjects. The values of forced vital capacity (107.1 ± 15.9 vs. 98.9 ± 21.4%; p = 0.028), total lung capacity – TLC (107.3 ± 12.9 vs. 93.7 ± 7.60%; p = 0.002), residual volume (114.1 ± 22.7 vs. 90.0 ± 14.6%; p < 0.001), and airways’ resistance (3.82 vs. 2.31 cmH2O/L/s; p = 0.039) were greater in acromegalic patients than in control subjects. The difference between the TLC measured by plethysmography and the VA (alveolar volume) measured during the DLCO maneuver was higher in acromegalic patients than in control subjects (0.69 ± 0.46 vs. 0.19 ± 0.61 L; p = 0.021). The main findings in HRCT in acromegalic patients were air trapping, airway calcification and bronchiectasis, which were observed in 60%, 40% and 35% of cases, respectively. There was no significant correlation between the levels of growth hormone and insulin-like growth factor I, the lung function and the air trapping.
Acromegalic patients show changes consistent with the involvement of the small airways and ventilation inhomogeneity, both in terms of lung function and structure. However, air trapping cannot be explained either by hormone levels or changes in lung function.
PMCID: PMC3831601  PMID: 24219873
Acromegaly; Respiratory function tests; Respiratory mechanics; Tomography
7.  Echocardiography may help detect pulmonary vasculopathy in the early stages of pulmonary artery hypertension associated with systemic sclerosis 
Pulmonary arterial hypertension (PAH) in patients with systemic sclerosis is associated with a poor prognosis, but this can be improved by early disease detection. Abnormal pulmonary and cardiac function can be detected early by means of echocardiography, whereas right heart catheterization is usually performed later.
The purpose of this prospective study was to detect early the presence of pulmonary artery vasculopathy in patients with verified systemic sclerosis without significant pulmonary fibrosis, normal lung volumes and a mildly reduced lung diffusion capacity of carbon monoxide (DLCO).
Nineteen consecutive female NYHA class I-II patients with scleroderma and a PAPs of < 35 mm/Hg measured by echocardiography, were enrolled between September 2007 and September 2009. They had a mean age of 51 ± 13 years, body mass index of 25 ± 5 kg/m2). They all underwent complete Doppler echocardiography, CPET, a pulmonary ventilation test (carbon monoxide lung diffusion, DLCO), HRCT. To investigate PAH by means of complete resting Doppler echocardiography estimates of systolic pulmonary artery pressure (PAPs) derived from tr icuspid regurgitation, mean PAP derived from pulmonary regurgitation, pulmonary vessel resistance (PVR) derived from the acceleration time of the pulmonary outflow tract (ACTpo), and right ventricular function derived from tricuspid annular plane systolic excursion (TAPSE). Right heart catheterisation was conducted only, if pulmonary hypertension was suggested by echocardiography and an abnormal ventilator test.
The data are given as mean values ± SD, unless otherwise stated. The correlations between the variables were analysed using Pearson's r coefficient, and the predictive value of the variables was calculated using linear regression analysis. A p value of > 0.05 was considered significant.
Right heart catheterization detected PAH in 15/19 patients; mean PAP was 30.5 mm/Hg and RVP 3.6 UW. Coronary angiography of the patients aged more than 55 years showed some evidence of significant coronary artery disease. Echocardiography showed high systolic PAP values (46 ± 8 mmHg), whereas right ventricular function was normal (TAPSE 23 ± 3 mm), and in line with the NYHA class. ACTpo was reduced in the patients with a systolic PAP of < 46 mm/Hg (p > 0.001) and positively correlated with DLCO (p > 0.001) and the hemodynamic data.
There was a good correlation between ACTpo and PVR (hemodynamic data) (r = -0615; p > 0.01).
Although they need to be confirmed by studies of larger series of patients, our findings suggest that, in comparison with hemodynamic data, non-invasive echocardiographic measurements are an excellent means of identifying early-stage PAH.
PMCID: PMC2908574  PMID: 20598164
8.  Selective Involvement of the Amygdala in Systemic Lupus Erythematosus 
PLoS Medicine  2006;3(12):e499.
Antibodies specifically affect the amygdala in a mouse model of systemic lupus erythematosus (SLE). The aim of our study was to investigate whether there is also specific involvement of the amygdala in human SLE.
Methods and Findings
We analyzed a group of 37 patients with neuropsychiatric SLE (NP-SLE), 21 patients with SLE, and a group of 12 healthy control participants with diffusion weighted imaging (DWI). In addition, in a subset of eight patients, plasma was available to determine their anti-NMDAR antibody status. From the structural magnetic resonance imaging data, the amygdala and the hippocampus were segmented, as well as the white and gray matter, and the apparent diffusion coefficient (ADC) was retrieved. ADC values between controls, patients with SLE, and patients with NP-SLE were tested using analysis of variance with post-hoc Bonferroni correction. No differences were found in the gray or white matter segments. The average ADC in the amygdala of patients with NP-SLE and SLE (940 × 10−6 mm2/s; p = 0.006 and 949 × 10−6 mm2/s; p = 0.019, respectively) was lower than in healthy control participants (1152 × 10−6 mm2/s). Mann-Whitney analysis revealed that the average ADC in the amygdala of patients with anti-NMDAR antibodies (n = 4; 802 × 10−6 mm2/s) was lower (p = 0.029) than the average ADC of patients without anti-NMDAR antibodies (n = 4; 979 × 10−6 mm2/s) and also lower (p = 0.001) than in healthy control participants.
This is the first study to our knowledge to observe damage in the amygdala in patients with SLE. Patients with SLE with anti-NMDAR antibodies had more severe damage in the amygdala compared to SLE patients without anti-NMDAR antibodies.
Patients with SLE who also had antibodies against the NMDA receptor had more severe damage in the amygdala as compared with patients with SLE without these antibodies.
Editors' Summary
The human body is continually attacked by viruses, bacteria, fungi, and parasites, but the immune system usually prevents these pathogens from causing disease. To be effective, the immune system has to respond rapidly to foreign antigens (bits of proteins that are unique to the pathogen) but ignore self-antigens. In autoimmune diseases, this ability to discriminate between self and nonself fails for unknown reasons, and the immune system begins to destroy human tissues. In the chronic autoimmune disease systemic lupus erythematosus (SLE or lupus), the immune system attacks the skin, joints, nervous system, and many other organs. Patients with SLE make numerous “autoantibodies” (antibodies are molecules made by the immune system that recognize and attack antigens; autoantibodies attack self-antigens). These autoantibodies start the attack on the body; then other parts of the immune system join in, causing inflammation and forming deposits of immune cells, both of which damage tissues. Common symptoms of SLE include skin rashes and arthritis, but some patients develop NP-SLE, a form of SLE that includes neuropsychiatric symptoms such as amnesia, dementia, mood disorders, strokes, and seizures. There is no cure for SLE, but mild cases are controlled with ibuprofen and other non-steroidal anti-inflammatory drugs; severe cases are kept in check with corticosteroids and other powerful immunosuppressants.
Why Was This Study Done?
In most of the tissues affected by SLE, the damage done by autoantibodies and immune cells can be seen when the tissues are examined with a microscope. But there is little microscopic damage visible in the brains of patients with NP-SLE. More generally, it is unclear how or even whether the immune system affects mental functions and emotion. In this study, researchers used magnetic resonance imaging (MRI) to investigate whether there are any structural changes in the brains of patients with NP-SLE that could explain their neuropsychiatric symptoms. They have also examined whether any changes in the brain can be linked to the presence of autoantibodies that recognize a protein called the NMDA receptor (anti-NMDAR antibodies) that is present on brain cells.
What Did the Researchers Do and Find?
The researchers used an MRI technique called diffusion weighted imaging to examine the brains of several patients with NP-SLE or SLE and the brains of several healthy individuals. Using this technique, it is possible to quantify the amount of structural damage in different regions of the brain. The researchers found no differences in most areas of the brain between the two groups of patients and the healthy controls. However, there were clear signs of damage in the amygdala (the part of the brain that regulates emotions and triggers responses to danger) in the patients with SLE or NP-SLE when compared to the control individuals. The researchers also found that the damage was more severe in the patients who had anti-NMDAR autoantibodies than in those that did not have these autoantibodies.
What Do These Findings Mean?
These findings suggest that autoantibodies produced by patients with SLE specifically damage the amygdala, a discovery that helps to explain some of the neuropsychiatric symptoms of this condition. Previous work has shown that the treatment of mice with anti-NMDAR antibodies and epinephrine, a stress hormone that causes leaks in the blood-brain barrier (antibodies can't usually get into the brain because of this barrier), results in damage to the amygdala and a deficient response to dangerous stimuli. The researchers suggest that a similar series of events might happen in SLE—patients often mention that a period of major stress precedes the development of symptoms. To provide stronger evidence for such a scenario, a detailed study of how stress relates to neuropsychiatric symptoms is needed. The damage to the amygdala (and the lack of damage elsewhere in the brain) and the possible association between brain damage and anti-NMDAR antibodies seen in this small study also need to be confirmed in more patients. Nevertheless, these findings provide an intriguing glimpse into the interplay between the immune system and the brain and into how stress might lead to physical damage in the brain.
Additional Information.
Please access these Web sites via the online version of this summary at
MedlinePlus encyclopedia pages on autoimmunity and on systemic lupus erythematosus
US National Institute of Arthritis and Musculoskeletal and Skin Diseases booklet for patients with SLE
American College of Rheumatology information for patients on SLE
NHS Direct Online Health Encyclopedia pages on SLE
The Lupus Foundation of America information and support for patients with SLE
PMCID: PMC1702559  PMID: 17177602
9.  The Bronchoalveolar Lavage Pattern in Radiation Pneumonitis Secondary to Radiotherapy for Breast Cancer 
Mædica  2010;5(4):250-257.
Background and purpose: Radiotherapy in breast cancer patients is limited by lung tissue tolerance. Two complications involving the lung are known: radiation pneumonitis (RP) and radiation fibrosis. The aim of the study was to evaluate the pattern of bronchoalveolar lavage (BAL) in patients with RP after radiotherapy for breast cancer in symptomatic and asymptomatic patients.
Material and methods: Sixty-five female patients (mean age 58.3 yrs) with RP after radiotherapy for breast cancer were included in the study. The majority of patients had previous breast surgery (mastectomy or lumpectomy and axillary dissection) and received doses of radiations of 45-50Gy. All patients had adjuvant chemotherapy with cyclophosphamide, 5-fluorouracil, and epirubicin or methotrexate.
Results: All patients had an infiltrate or consolidation on chest radiography confined to the upper lobe of the irradiated lung, as marker of RP. Based on the presence or absence of symptoms, we divided the patients in 2 groups: 49 patients (75.4%) with symptomatic RP (fever, cough, dyspnea, chest pain and fatigue) and 16 patients (24.6%) without any symptom. Symptomatic RP patients had a BAL with significant increase in total cells (18.0±12.2 x106 cells•100mL-1) when compared to BAL in asymptomatic patients (11.9±6.2 x106 cells•100mL-1), p=0.01. Lymphocytosis in BAL was significantly increased in symptomatic group, compared with asymptomatic one (35.4±18.7% vs. 26.1±14.3%, p=0.045), with predominance of T lymphocytes (CD3). It was also a predominance of CD4 lymphocytes in all patients, but the CD4/CD8 ratio was inside normal range in the majority of cases. Five patients had clinical features of bronchiolitis obliterans organizing pneumonia (BOOP) secondary to irradiation with increased percentages of lymphocytes, neutrophils, eosinophils, and mast cells in BAL and one patient without history of atopic disease had a percentage of 40% eosinophils. Only a mild reduction in diffusing capacity for carbon monoxide was seen in both groups on pulmonary function tests. The lung volumes were normal in all patients.
Conclusions: Lymphocytic alveolitis was the marker of radiation pneumonitis in all patients. The degree of the inflammatory reaction of the lungs was correlated with the presence of symptoms. The lymphocytic alveolitis consisted mainly of T lymphocytes, with a predominance of CD4 subset in both groups, but the CD4/CD8 ratio remained mostly into normal range.
PMCID: PMC3152839  PMID: 21977166
radiation pneumonitis; breast cancer; bronchoalveolar lavage; lymphocytosis
10.  Alveolar Gas Exchange and Pulmonary Functions in Patients with Type II Diabetes Mellitus 
Background: The incidence of diabetes is increasing tremendously throughout the world especially in the developing countries. This disease affects various organs like eyes, nerves, kidneys and the heart. In this study, we investigated whether lungs are also one of the target organs of diabetes mellitus or not.
Aim: To assess the pulmonary function parameters including alveolar gas exchange in patients with Type 2 Diabetes mellitus and to find the influence of hyperglycaemia and duration of diabetes.
Methodology: This cross sectional study involved 30 type II diabetic patients of age 30-60 years attending the diabetic outpatient department of SRM Medical College & Research Centre and 30 age and sex matched non-diabetic subjects as controls. The glycated haemoglobin (HbA1c) levels, fasting and post prandial blood glucose levels, pulmonary function parameters such as Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV1), Forced Expiratory Volume Percentage (FEV1 /FVC), Peak Expiratory Flow Rate (PEFR), Forced Expiratory Flow (25 – 75%), Peak Inspiratory flow ( PIF), Forced Inspiratory Vital Capacity ( FIVC), Total Lung Capacity ( TLC),Diffusing capacity of lung for carbon monoxide( DLCO) were measured for all the participants using Easyone Pro computerised spirometer. DLCO was measured by single breath Carbon Monoxide (CO) diffusion test. The alveolar membrane permeability was assessed by evaluating the ratio of DLCO to Alveolar Ventilation (VA).
Results: The pulmonary function parameters FVC, FEV1, PEFR, PIF, FIVC, TLC , DLCO and DLCO/VA were significantly low (p<0.05) in patients with type II diabetes mellitus when compared to control group. The DLCO and DLCO/VA were significantly lower (p<0.05) in patients with poor glycemic control(HbA1c > 7).
Conclusion: We conclude that the pulmonary function parameters like FVC, FEV1, PEFR, PIF, FIVC, TLC and alveolar gas exchange were significantly reduced in patients with type II diabetes. The patients with Type II diabetes mellitus had a restrictive pattern of respiratory abnormality. The patients with poor glycaemic control( HbA1c > 7) had reduced alveolar diffusion which was not dependent on the duration of diabetes. The impaired respiratory function may give way for the development of pulmonary complications. Spirometry can be used as a screening tool among diabetics as an early preventive measure.
PMCID: PMC3809625  PMID: 24179886
Alveolar gas exchange; Pulmonary Function Tests; Type II Diabetes Mellitus
11.  Efficacy and Safety of Sirolimus in Lymphangioleiomyomatosis 
The New England journal of medicine  2011;364(17):1595-1606.
Lymphangioleiomyomatosis (LAM) is a progressive, cystic lung disease in women; it is associated with inappropriate activation of mammalian target of rapamycin (mTOR) signaling, which regulates cellular growth and lymphangiogenesis. Sirolimus (also called rapamycin) inhibits mTOR and has shown promise in phase 1–2 trials involving patients with LAM.
We conducted a two-stage trial of sirolimus involving 89 patients with LAM who had moderate lung impairment — a 12-month randomized, double-blind comparison of sirolimus with placebo, followed by a 12-month observation period. The primary end point was the difference between the groups in the rate of change (slope) in forced expiratory volume in 1 second (FEV1).
During the treatment period, the FEV1 slope was −12±2 ml per month in the placebo group (43 patients) and 1±2 ml per month in the sirolimus group (46 patients) (P<0.001). The absolute between-group difference in the mean change in FEV1 during the treatment period was 153 ml, or approximately 11% of the mean FEV1 at enrollment. As compared with the placebo group, the sirolimus group had improvement from baseline to 12 months in measures of forced vital capacity, functional residual capacity, serum vascular endothelial growth factor D (VEGF-D), and quality of life and functional performance. There was no significant between-group difference in this interval in the change in 6-minute walk distance or diffusing capacity of the lung for carbon monoxide. After discontinuation of sirolimus, the decline in lung function resumed in the sirolimus group and paralleled that in the placebo group. Adverse events were more common with sirolimus, but the frequency of serious adverse events did not differ significantly between the groups.
In patients with LAM, sirolimus stabilized lung function, reduced serum VEGF-D levels, and was associated with a reduction in symptoms and improvement in quality of life. Therapy with sirolimus may be useful in selected patients with LAM. (Funded by the National Institutes of Health and others; MILES number, NCT00414648.)
PMCID: PMC3118601  PMID: 21410393
12.  An autopsy study of combined pulmonary fibrosis and emphysema: correlations among clinical, radiological, and pathological features 
BMC Pulmonary Medicine  2014;14:104.
Clinical evaluation to differentiate the characteristic features of pulmonary fibrosis and emphysema is often difficult in patients with combined pulmonary fibrosis and emphysema (CPFE), but diagnosis of pulmonary fibrosis is important for evaluating treatment options and the risk of acute exacerbation of interstitial pneumonia of such patients. As far as we know, it is the first report describing a correlation among clinical, radiological, and whole-lung pathological features in an autopsy cases of CPFE patients.
Experts retrospectively reviewed the clinical charts and examined chest computed tomography (CT) images and pathological findings of an autopsy series of 22 CPFE patients, and compared these with findings from 8 idiopathic pulmonary fibrosis (IPF) patients and 17 emphysema-alone patients.
All patients had a history of heavy smoking. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC%) was significantly lower in the emphysema-alone group than the CPFE and IPF-alone groups. The percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) was significantly lower in the CPFE group than the IPF- and emphysema-alone groups. Usual interstitial pneumonia (UIP) pattern was observed radiologically in 15 (68.2%) CPFE and 8 (100%) IPF-alone patients and was pathologically observed in all patients from both groups. Pathologically thick-cystic lesions involving one or more acini with dense wall fibrosis and occasional fibroblastic foci surrounded by honeycombing and normal alveoli were confirmed by post-mortem observation as thick-walled cystic lesions (TWCLs). Emphysematous destruction and enlargement of membranous and respiratory bronchioles with fibrosis were observed in the TWCLs. The cystic lesions were always larger than the cysts of honeycombing. The prevalence of both radiological and pathological TWCLs was 72.7% among CPFE patients, but no such lesions were observed in patients with IPF or emphysema alone (p = 0.001). The extent of emphysema in CPFE patients with TWCLs was greater than that in patients without such lesions. Honeycombing with emphysema was also observed in 11 CPFE patients.
TWCLs were only observed in the CPFE patients. They were classified as lesions with coexistent fibrosing interstitial pneumonia and emphysema, and should be considered an important pathological and radiological feature of CPFE.
PMCID: PMC4100038  PMID: 24972672
Thick-walled cystic lesion; Combined pulmonary fibrosis and emphysema; Autopsy; Idiopathic pulmonary fibrosis; Emphysema; Fibroblastic foci
13.  Diffuse Alveolar Hemorrhage: A Rare Life-Threatening Condition in Systemic Lupus Erythematosus 
Case Reports in Pulmonology  2012;2012:836017.
Diffuse alveolar hemorrhage (DAH) is a rare life-threatening complication in systemic lupus erythematosus (SLE) associated with high mortality rates. DAH is more common in women, and mean age of onset is around 30 years. It mostly occurs in patients with established diagnosis of SLE but can be the initial presentation of lupus in approximately 20%. DAH should be suspected in lupus patient presenting with new pulmonary infiltrates, decline in hemoglobin, hemoptysis, dyspnea, hypoxemia, and increase in carbon monoxide diffusion capacity. Radiographic evidence of bilateral pulmonary alveolar infiltrates that are usually perihilar or basilar with sparing of apices is seen. DAH can often mimic clinically and radiologically severe pneumonia or ARDS. Treatment includes high-dose corticosteroids, cyclophosphamide, and plasmapheresis. We report a case of diffuse alveolar hemorrhage complicating SLE flare-up in a male patient.
PMCID: PMC3420594  PMID: 22934226
14.  Effect of Cardiac Resynchronization Therapy on Pulmonary Function in Patients With Heart Failure 
The American journal of cardiology  2013;112(6):838-842.
Pulmonary congestion due to heart failure causes abnormal lung function. Cardiac resynchronization therapy (CRT) is a proven effective treatment for heart failure. The aim of this study was to test the hypothesis that CRT promotes increased lung volumes, bronchial conductance, and gas diffusion. Forty-four consecutive patients with heart failure were prospectively investigated before and after CRT. Spirometry, gas diffusion (diffusing capacity for carbon monoxide), cardiopulmonary exercise testing, New York Heart Association class, brain natriuretic peptide, the left ventricular ejection fraction, left atrial volume, and right ventricular systolic pressure were assessed before and 4 to 6 months after CRT. Pre- and post-CRT measures were compared using either paired Student’s t tests or Wilcoxon’s matched-pair test; p values <0.05 were considered significant. Improved New York Heart Association class, left ventricular ejection fraction, left atrial volume, right ventricular systolic pressure, and brain natriuretic peptide were observed after CRT (p <0.05 for all). Spirometry after CRT demonstrated increased percentage predicted total lung capacity (90 ± 17% vs 96 ± 15%, p <0.01) and percentage predicted forced vital capacity (80 ± 19% vs 90 ± 19%, p <0.01). Increased percentage predicted total lung capacity was significantly correlated with increased peak exercise end-tidal carbon dioxide (r = 0.43, p = 0.05). Increased percentage predicted forced vital capacity was significantly correlated with decreased right ventricular systolic pressure (r = −0.30, p = 0.05), body mass index (r =−0.35, p =0.02) and creatinine (r =−0.49, p =0.02), consistent with an association of improved bronchial conductance and decreased congestion. Diffusing capacity for carbon monoxide did not significantly change. In conclusion, increased lung volumes and bronchial conductance due to decreased pulmonary congestion and increased intrathoracic space contribute to an improved breathing pattern and decreased hyperventilation after CRT. Persistent alveolar-capillary membrane remodeling may account for unchanged diffusing capacity for carbon monoxide.
PMCID: PMC3919510  PMID: 23747043
15.  Lung involvement in primary Sjögren's syndrome is mainly related to the small airway disease 
OBJECTIVE—To evaluate lung involvement in patients with primary Sjögren's syndrome.
METHODS—Sixty one consecutive, non-smoking patients, 58 women and three men, were evaluated clinically, physiologically, and radiologically. A bronchial and/or transbronchial biopsy was performed on 13 of the patients. Physiological data were compared with that of a control group of 53 healthy non-smoking subjects matched for age and sex.
RESULTS—In 41% of the patients the main symptom was dry cough. Physiological studies revealed that the patients presented significantly lower expiratory flow values (% pred) when compared with those of the control group: the forced expiratory volume in one second (FEV1) (mean (SD)) was 96% (16) v 111% (13) (p<0.0001), the maximal expiratory flow at the 50% of the vital capacity (MEF50) was 72% (24) v 103% (17) (p<0.0001), and the maximal expiratory flow at the 25% of the vital capacity (MEF25) was 49% (25) v 98 % (20) (p<0.0001). No significant difference was noted for the carbon monoxide diffusion value (% pred), between patients and controls. Blood gases were evaluated in 44 patients: mild hypoxemia was observed, and the alveolo-arterial oxygen difference (P(A-a)O2) correlated significantly with MEF50 (r=0.35, p<0.01) and MEF25 (r=0.33, p<0.01) values. Chest radiography showed mild, interstitial-like changes in 27 patients while slightly increased markings were present in 21. High resolution computed tomography of the lungs was performed in 32 patients (four with a normal chest radiograph, six with suspected interstitial pattern, 19 with apparent interstitial pattern, and three with hyperinflation) and revealed predominantly wall thickening at the segmental bronchi. All positive findings by computed tomography derived from the patients with abnormal chest radiographs. Transbronchial and/or endobronchial biopsy specimens in 10 of the 11 sufficient tissue samples revealed peribronchial and/or peribronchiolar mononuclear inflammation, while interstitial inflammation coexisted in two patients.
CONCLUSION—The airway epithelia seem to be the main target of the inflammatory lesion of the lung in patients with primary Sjögren's syndrome. It seems to be common, subclinically leading to obstructive small airway physiological abnormalities.

 Keywords: small airway obstruction; computed tomography; autoimmune rheumatic disorders
PMCID: PMC1752755  PMID: 10343542
16.  Exhaled IL-8 in Systemic Lupus Erythematosus with and without Pulmonary Fibrosis 
The purpose of this study is to evaluate the relationship between the concentration of interleukin-8 (IL-8) in exhaled breath condensate (EBC) and bronchoalveolar lavage fluid (BALF) with the disease activity score and pulmonary function of systemic lupus erythematosus (SLE) patients with and without pulmonary fibrosis. Thirty-four SLE patients and 31 healthy controls were enrolled and evaluated using high-resolution computed tomography (HRCT), pulmonary function tests, systemic lupus activity measure (SLAM), assessing BALF and EBC. IL-8 levels in BALF and EBC samples were measured with an enzyme-immunosorbent assay kit. The mean (±SEM) IL-8 concentrations in BALF and EBC were higher in SLE patients compared to healthy controls (34.84 ± 95.0 vs. 7.65 ± 21.22 pg/ml, p < 0.001; 3.82 ± 0.52 pg/m vs. 1.7 ± 1.7 pg/ml, p < 0.001, respectively). SLE patients had increased percentage of neutrophils in BALF when compared with control group (1.00 ± 5.99 vs. 0.00 ± 0.56 %, p = 0.0003). Pulmonary fibrosis in HRCT was found in 50 % of SLE patients. The disease activity scored by SLAM was significantly higher and total lung capacity was significantly lower in SLE patients with pulmonary fibrosis (8.00 ± 3.17 vs. 6.00 ± 2.31, p = 0.01; 88.00 ± 28.29 vs. 112.00 ± 21.08 % predicted, p = 0.01, respectively). In SLE patients with pulmonary fibrosis, correlations were found between SLAM and IL-8 concentration in BALF, forced expiratory volume in 1 s and forced vital capacity (r = 0.65, p = 0.006; r = −0.53, p = 0.035; r = −0.67, p = 0.006, respectively). Our results indicate that IL-8 plays an important role in the pathogenesis of SLE. An increased concentration of IL-8 according to BALF could be considered as a useful biomarker of SLE activity and pulmonary fibrosis in SLE.
PMCID: PMC4024123  PMID: 24492930
Systemic lupus erythematosus; Interleukin-8; Exhaled breath condensate; Bronchoalveolar lavage fluid; Pulmonary fibrosis
17.  Impact of severe acute respiratory syndrome (SARS) on pulmonary function, functional capacity and quality of life in a cohort of survivors 
Thorax  2005;60(5):401-409.
Objective: To examine the impact of severe acute respiratory syndrome (SARS) on pulmonary function, exercise capacity, and health-related quality of life (HRQoL) among survivors.
Methods: 110 survivors with confirmed SARS were evaluated at the Prince of Wales Hospital, HK at the end of 3 and 6 months after symptom onset. The assessment included lung volumes (TLC, VC, RV, FRC), spirometry (FVC, FEV1), carbon monoxide transfer factor (TLCO adjusted for haemoglobin), inspiratory and expiratory respiratory muscle strength (Pimax and Pemax), 6 minute walk distance (6MWD), chest radiographs, and HRQoL by SF-36 questionnaire.
Results: There were 44 men and 66 women with a mean (SD) age of 35.6 (9.8) years and body mass index of 23.1 (4.8) kg/m2. Seventy (64%) were healthcare workers. At 6 months 33 subjects (30%) had abnormal chest radiographs; four (3.6%), eight (7.4%), and 17 (15.5%) patients had FVC, TLC, and TLCO below 80% of predicted values; and 15 (13.9%) and 24 (22.2%) had Pimax and Pemax values below 80 cm H2O, respectively. The 6MWD increased from a mean (SD) of 464 (83) m at 3 months to 502 (95) m (95% CI 22 to 54 m, p<0.001), but the results were lower than normal controls in the same age groups. There was impairment of HRQoL at 6 months. Patients who required ICU admission (n = 31) had significantly lower FVC, TLC, and TLCO than those who did not.
Conclusion: The exercise capacity and health status of SARS survivors was considerably lower than that of a normal population at 6 months. Significant impairment in surface area for gas exchange was noted in 15.5% of survivors. The functional disability appears out of proportion to the degree of lung function impairment and may be related to additional factors such as muscle deconditioning and steroid myopathy.
PMCID: PMC1758905  PMID: 15860716
18.  An assessment of lung volumes and gas transfer in sickle-cell anaemia 
Thorax  1971;26(3):309-315.
Lung volumes, gas transfer, and anthropometry were assessed in sickle-cell anaemia in 13 patients with previous pulmonary episodes and 12 without this history. Respiratory symptoms were assessed with a standard questionnaire, total lung capacity and its subdivisions, the carbon monoxide transfer factor (TF), diffusion capacity of the alveolar capillary membrane (Dm), and the alveolar capillary blood volume (Vc) were measured, and stature, sitting height and chest diameters were recorded. Total lung capacity and vital capacity were reduced because the thorax was small relative to body size in these patients.
TF was reduced by anaemia, small lungs, and a low Dm which was not simply a consequence of small lungs. This reduction tended to be offset by an increase in Vc. The cause of the reduction in Dm above that due to small lungs was probably located in the pulmonary circulation. Anaemia was considered unlikely to be responsible, and although a difference between the reactivity of carbon monoxide with Hb A and Hb S may have contributed to the reduction in Dm and the increase in Vc, it was thought unlikely to be the only cause: Dm was significantly lower in patients with a history of pulmonary complications and in non-smokers than in those without this history and in smokers. Alveolar capillary collapse or occlusion may also have reduced Dm in sickle-cell anaemia and accounted for the greater reductions in those with previous pulmonary episodes and in non-smokers.
PMCID: PMC1019088  PMID: 5089498
19.  Lung structure and function in cigarette smokers. 
Thorax  1994;49(5):473-478.
BACKGROUND--Cigarette smoking produces an inflammatory response in the airways of everyone but only 15-20% of smokers develop airways obstruction. The present study concerns the relative importance of peripheral airways inflammation and the emphysematous destruction of the parenchymal support of the airways in the pathogenesis of this obstruction. METHODS--A total of 407 patients with a diagnosis of lung tumour performed pulmonary function tests a day or two before a lung or lobar resection. The specimens were fixed in inflation and analysed at the gross and microscopic level to determine the extent and severity of the emphysematous process, the number of alveoli supporting the outer walls of the airways, and the average distance between alveolar walls. The severity of the inflammatory process in the respiratory and nonrespiratory bronchioles was also assessed using a previously established grading system. RESULTS--The lung function test showed that a decline in FEV1 was associated with an increase in residual volume and a decrease in the diffusing capacity for carbon monoxide and a reduction in the lung maximum elastic recoil pressure. The prevalence of grossly visible emphysema increased as FEV1 declined, but the extent and severity of these lesions and the number of alveoli supporting the outer walls of the peripheral airways was similar at all levels of FEV1. The system used to grade inflammatory response in the peripheral airways failed to identify a specific defect responsible for the physiological abnormalities. CONCLUSION--The reduction in FEV1 associated with chronic cigarette smoking can be partially explained by loss of lung elastic recoil pressure which reduces the force driving air out of the lung. This loss of elastic recoil pressure is attributed to microscopic enlargement of the air spaces rather than to grossly visible emphysema. The exact nature of the lesions responsible for the peripheral airways obstruction remains to be identified.
PMCID: PMC474869  PMID: 8016769
20.  The Burden of Image Based Emphysema and Bronchiolitis in HIV-Infected Individuals on Antiretroviral Therapy 
PLoS ONE  2014;9(10):e109027.
With the widespread use of anti-retroviral therapy (ART), individuals infected with human immune deficiency virus (HIV) are increasingly experiencing morbidity and mortality from respiratory disorders. However, the prevalence or the risk factors associated with emphysema and bronchiolitis are largely unknown.
Thoracic computed tomography (CT) scans were performed in 1,446 patients infected with HIV who were on ART and who attended a tertiary care metabolic clinic (average age 48 years and 29% females). Detailed history and physical examination including anthropometric measurements were performed. Complete pulmonary function tests were performed in a subset of these patients (n = 364). No subjects were acutely ill with a respiratory condition at the time of CT scanning.
Nearly 50% of the subjects had CT evidence for emphysema, bronchiolitis or both with 13% (n = 195) showing bronchiolitis, 19% (n = 274) showing emphysema and 16% (n = 238) revealing both. These phenotypes were synergistically associated with reduced regular physical activity (p for interaction <.0001). The most significant risk factors for both phenotypes were cigarette smoking, intravenous drug use and peripheral leucocytosis. Together, the area-under-the curve statistics was 0.713 (p = 0.0037) for discriminating those with and without these phenotypes. There were no significant changes in lung volumes or flow rates related to these phenotypes, though the carbon monoxide diffusion capacity was reduced for the emphysema phenotype.
Emphysema and bronchiolitis are extremely common in HIV-infected patients who are treated with ART and can be identified by use of thoracic CT scanning.
PMCID: PMC4212912  PMID: 25354261
21.  Decrease in pulmonary function during bleomycin-containing combination chemotherapy for testicular cancer: not only a bleomycin effect. 
British Journal of Cancer  1995;71(1):120-123.
This study was performed to determine the changes in pulmonary function in patients randomised to receive treatment with four cycles of bleomycin, etoposide and cisplatin (BEP) (27 patients) or with four cycles of etoposide and cisplatin (EP) (27 patients) for disseminated non-seminomatous testicular cancer. This enabled us to establish whether effects other than those due to bleomycin determined the detrimental effects of BEP on lung function assessments. Slow inspiratory vital capacity (VC), the transfer factor of the lungs for carbon monoxide (TLCO), the diffusing capacity of the alveolo-capillary membrane (Dm), the pulmonary capillary blood volume (Vc) and the transfer factor of the lungs for carbon monoxide per unit alveolar volume (KCO) were determined before and at 3 week intervals during chemotherapy. Both groups, similar in terms of factors that may influence pulmonary function, showed during therapy a significant decrease in TLCO compared with the pretreatment value. Only at the end of the therapy was a significant difference in TLCO between both groups observed. Dm diminished also significantly in both groups during treatment, but differences between both groups were not seen. VC and Vc decreased in patients receiving BEP but remained constant during treatment with EP. It can be concluded that the Dm, KCO, and the widely used TLCO are not suitable parameters to monitor specifically pulmonary toxicity induced by bleomycin as part of a multidrug regimen. However, VC and Vc appear to be proper lung function assessments which reflect specifically alterations induced by bleomycin.
PMCID: PMC2033457  PMID: 7529523
22.  Pulmonary Function after Whole Lung Irradiation in Pediatric Patients with Solid Malignancies 
Cancer  2011;118(5):1450-1456.
Although whole lung irradiation (WLI) is used to treat pulmonary metastases of pediatric solid malignancies, few studies have addressed its long-term pulmonary consequences.
We conducted a retrospective study of longitudinal changes in 171 pulmonary function tests (PFTs) and their relationship with clinical features in 48 survivors of pediatric malignant solid tumors treated with WLI.
Although active respiratory symptoms were seen in only 9 (18.8%) patients, abnormalities in forced vital capacity (FVC; 58.3%), forced expiratory volume in 1 second (FEV1; 64.6%), total lung capacity (TLC; 72.9%), and diffusion capacity of carbon monoxide corrected for hemoglobin (DLCOcorr; 70.8%) were common. At a median follow-up of 9.7 years after WLI, FVC, FEV1, and TLC significantly declined longitudinally (P = .04, .03, and .02, respectively). Focal pulmonary boost irradiation was significantly associated with abnormal FEV1/FVC (P = .03), forced expiratory flow between 25% and 75% forced vital capacity (FEF25%–75%; P = .005), residual volume (RV; P = .005), and RV/TLC (P = .002). Ten patients had baseline PFTs, and FVC, FEV1, TLC and DLCOcorr worsened immediately after radiation, followed by transient improvement but subsequent decline. Thirteen of 32 (40.6%) patients over the age of 18 were smokers.
Pulmonary dysfunction, especially in lung volumes, was prevalent after WLI and worsened over time although most patients were asymptomatic. Boost irradiation impaired pulmonary function, and a significant proportion of patients were smokers. Further studies are planned to assess the predictors and clinical consequences of progressive PFT abnormalities and to evaluate educational interventions.
PMCID: PMC3233655  PMID: 21800284
pulmonary function tests; solid tumor; whole lung irradiation; pediatric cancer; follow-up
23.  Six minute walking test and carbon monoxide diffusing capacity for non-small cell lung cancer: easy performed tests in every day practice 
Journal of Thoracic Disease  2012;4(6):569-576.
Several studies have demonstrated that reduced lung function is a significant risk factor for lung cancer and increased surgical risk in patients with operable stages of lung cancer. The aim of the study was to perform pulmonary function tests and investigate which is a favorable respiratory function test for overall survival between lung cancer stages.
Lung function tests were performed to lung cancer patients with non-small cell lung cancer of stage I, II, III and IV (241 patients in total). They had the last follow-up consecutively between December 2006 and July 2008. The staging was decided according to the sixth edition of TNM classification of NSCLC. The Forced Expiratory Volume in 1sec (FEV1), Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) were measured according to American Thoracic Society/European Respiratory Society guidelines. The 6 Minute Walking Test (6MWT) was measured according to the American Thoracic Society.
There was a significant association of the DLCO upon diagnosis and overall survival for stage II (P<0.007) and IV (P<0.003). Furthermore, there was a significant association between 6MWT and overall survival for stage III (P<0.001) and stage IV (P<0.010).
The significance for each lung function test is different among the stages of NSCLC. DLCO and 6MWT upon admission are the most valuable prognostic factors for overall survival of NSCLC.
PMCID: PMC3506801  PMID: 23205280
24.  AB 40. Six minute walking test and DLCO for non-small cell lung cancer. Easy performed tests in every day practice 
Journal of Thoracic Disease  2012;4(Suppl 1):AB40.
Several studies have demonstrated that reduced lung function is a significant risk factor for lung cancer and increase surgical risk in patients with operable stages of lung cancer. The aim of the study was to perform pulmonary function tests and investigate which is a favorable respiratory function test for overall survival between lung cancer stages.
Lung function tests were performed to lung cancer patients with non-small cell lung cancer of stage I, II, III and IV (241 patients in total). They had the last follow-up consecutively between December 2006 and July 2008. The staging was decided according to the sixth edition of TNM classification of NSCLC. The Forced Expiratory Volume in 1sec (FEV1), Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) were measured according to American Thoracic Society/European Respiratory Society guidelines. The 6 Minute Walking Test (6MWT) was measured according to the American Thoracic Society.
There was a significant association of the DLCO upon diagnosis and overall survival for stage II (P<0.007) and IV (P<0.003). Furthermore, there was a significant association between 6MWT and overall survival for stage III (P<0.001) and stage IV (P<0.010).
The significance for each lung function test is different among the stages of NSCLC. DLCO and 6MWT upon admission are the most valuable prognostic factors for overall survival of NSCLC.
PMCID: PMC3537340
25.  Analysis of longitudinal changes in dyspnea of patients with chronic obstructive pulmonary disease: an observational study 
Respiratory Research  2012;13(1):85.
Guidelines recommend that symptoms as well as lung function should be monitored for the management of patients with chronic obstructive pulmonary disease (COPD). However, limited data are available regarding the longitudinal change in dyspnea, and it remains unknown which of relevant measurements might be used for following dyspnea.
We previously consecutively recruited 137 male outpatients with moderate to very severe COPD, and followed them every 6 months for 5 years. We then reviewed and reanalyzed the data focusing on the relationships between the change in dyspnea and the changes in other clinical measurements of lung function, exercise tolerance tests and psychological status. Dyspnea with activities of daily living was assessed with the Oxygen Cost Diagram (OCD) and modified Medical Research Council dyspnea scale (mMRC), and two dimensions of disease-specific health status questionnaires of the Chronic Respiratory Disease Questionnaire (CRQ) and the St. George’s Respiratory Questionnaire (SGRQ) were also used. Dyspnea at the end of exercise tolerance tests was measured using the Borg scale.
The mMRC, CRQ dyspnea and SGRQ activity significantly worsened over time (p < 0.001), but the OCD did not (p = 0.097). Multiple regression analyses revealed that the changes in the OCD, mMRC, CRQ dyspnea and SGRQ activity were significantly correlated to changes in forced expiratory volume in one second (FEV1) (correlation of determination (r2) = 0.05-0.19), diffusing capacity for carbon monoxide (r2 = 0.04-0.08) and psychological status evaluated by Hospital Anxiety and Depression Scale (r2 = 0.14-0.17), although these correlations were weak. Peak Borg score decreased rather significantly, but was unrelated to changes in clinical measurements.
Dyspnea worsened over time in patients with COPD. However, as different dyspnea measurements showed different evaluative characteristics, it is important to follow dyspnea using appropriate measurements. Progressive dyspnea was related not only to progressive airflow limitation, but also to various factors such as worsening of diffusing capacity or psychological status. Changes in peak dyspnea at the end of exercise may evaluate different aspects from other dyspnea measurements.
PMCID: PMC3519563  PMID: 23006638
COPD; Dyspnea; Airflow limitation; Diffusing capacity; Exercise; Psychological status; Disease progression

Results 1-25 (1203404)