Impact of interstitial lung disease on surgical morbidity and mortality for lung cancer: analyses of short-term and long-term outcomes

BACKGROUND: This study investigated postoperative morbidity, mortality, and the long-term survival for patients with lung cancer who have interstitial lung diseases. METHODS: A retrospective chart review of 931 patients with lung cancer who underwent pulmonary resection at Chiba University Hospital between 1990 and 2000 was undertaken. Interstitial lung disease was defined by medical history, physical examination, and abnormalities compatible with bilateral lung fibrosis on chest computed tomography or high-resolution computed tomography (36 patients: 3.9%, interstitial lung diseases group). The remaining 895 patients (96.1%) were categorized as non-interstitial lung disease group. RESULTS: The incidence of postoperative pneumonia and acute or exacerbation of interstitial pneumonia was higher in the interstitial lung disease group (all P <.05). Thirty-day mortality was statistically equivalent between the interstitial lung disease and the non-interstitial lung disease groups (P =.30). The 5-year overall survivals were 62.5% (non-interstitial lung disease) and 35.6% (interstitial lung disease). Respiratory failure was the second main cause of death after the recurrence of primary cancer in the interstitial lung disease group. The risk factors for long-term mortality were interstitial lung diseases, advanced pathologic stage, male sex, high age, and positive smoking history (all P <.05). CONCLUSIONS: Interstitial lung disease was a risk factor for developing postoperative morbidity and mortality and poor long-term survival due to the occurrence of respiratory failure.     

Bronchoalveolar lavage in patients with mild and severe rheumatoid lung disease.

The reported prevalence of interstitial lung disease in patients with rheumatoid arthritis has varied from 10% to 50%, yet less than 5% of patients with arthritis develop severe fibrosing interstitial lung disease. This suggests that subclinical disease may not always presage progressive disease. Bronchoalveolar lavage fluid from patients with rheumatoid arthritis and either clinically evident interstitial lung disease or subclinical disease was examined for the presence of factors with a putative role in the development of interstitial fibrosis. Patients with subclinical disease were identified by prospective radiographic and lung function screening of 93 patients with rheumatoid arthritis. Fourteen patients were identified in this manner and an association between subclinical disease and smoking history was noted. Eleven patients with established interstitial lung disease had increased neutrophils (p less than 0.05), collagenase, and type III procollagen N terminal peptide levels (p less than 0.01) in the bronchoalveolar lavage fluid. Preliminary characterisation of the bronchoalveolar lavage collagenase suggested that it originated from neutrophils. Ten patients with subclinical interstitial lung disease underwent bronchoalveolar lavage. Of these, one had increased neutrophils and two had increased collagenase concentrations--abnormalities associated with advanced interstitial lung disease and a poor prognosis. These results suggest that in arthritis patients with evidence of subclinical pulmonary interstitial disease bronchoalveolar lavage might be useful in identifying those who may require careful monitoring in the hope that early treatment will prevent severe fibrosis.     

Exacerbation of interstitial lung disease during etanercept therapy: Two cases

We report two cases of interstitial lung disease possibly related to TNF alpha antagonist therapy (etanercept) in patients with rheumatoid arthritis. In both cases, pre-existing interstitial lung disease worsened during etanercept therapy. We found 19 previously published cases of interstitial lung disease in patients who were taking TNF alpha antagonists and had no evidence of infection, raising the possibility of a causal link with the medication. The potential pathophysiological mechanisms remain unknown. Caution is in order when using TNF alpha antagonists in patients with pre-existing lung disease. The development or exacerbation of interstitial lung disease in a patient on TNF alpha antagonist therapy should lead to investigations for a cause. Should these investigations prove negative, the treatment must be discontinued.     

Accuracy of mortality data for interstitial lung diseases in New Mexico, USA.

BACKGROUND: The sensitivity and accuracy of death certificates and mortality data as sources of population based data on the occurrence of interstitial lung diseases has received limited attention. To determine the usefulness of these data sources, death certificates and mortality data from patients in New Mexico were examined. METHODS: Patients with an interstitial lung disease were identified from a population based registry. For subjects who had died, diagnostic information from their death certificates and from mortality data was compared with the clinical diagnoses made before death. RESULTS: Of 385 patients with a clinical diagnosis of an interstitial lung disease, 134 died between October 1988 and August 1994. Death certificates were obtained for 96% of these patients. An interstitial lung disease was listed somewhere on the death certificate for only 46% of the patients, and as an immediate cause of death for only 15%. For the patients with an interstitial lung disease listed somewhere on the death certificate the overall concordance between the diagnoses before death and those on the death certificate was 76%. Mortality data for the State of New Mexico showed a diagnosis of interstitial lung disease to be the assigned cause of death for only 22% of the patients. The overall agreement between the diagnoses made before death and those of the state mortality data was only 21%. CONCLUSIONS: These results suggest that death certificates and state mortality data are neither sensitive nor accurate for describing the occurrence of interstitial lung diseases. This finding may partly explain the apparently low mortality rates from idiopathic pulmonary fibrosis in the USA compared with other countries.     

Clinical significance of respiratory bronchiolitis on open lung biopsy and its relationship to smoking related interstitial lung disease

BACKGROUND: Respiratory bronchiolitis-associated interstitial lung disease (RBILD) is a rare form of interstitial lung disease which may present in similar fashion to other types of chronic interstitial pneumonia. The purpose of this study was to undertake a clinicopathological review of 10 patients with RBILD and to examine the clinical and imaging data related to its histopathological pattern, in particular the relationship of RBILD to smoking. METHODS: Thirteen out of 168 retrospectively reviewed patients, from whom biopsy specimens were taken for suspected diffuse lung disease, were identified with a histopathological pattern of RBILD. Three cases were rejected as follow up data were unavailable. The 10 remaining cases constituted the study group and both clinical and imaging data were collected from patients' notes and referring physicians. RESULTS: Histopathologically, four cases of RBILD overlapped with the pattern of desquamative interstitial pneumonitis (DIP) and nine also had microscopic evidence of centrilobular emphysema. Nine patients were smokers, ranging from 3 to 80 pack years. The one non-smoker had an occupational exposure to the fumes of solder flux. The sex distribution was equal with an age range of 32-65 years. Two patients were clubbed. Lung function tests showed both restrictive and obstructive patterns together with severe reductions in carbon monoxide transfer factor in seven patients. Chest radiographs showed reticular or reticulonodular infiltrates in five patients and a ground glass pattern in two. CT scans were consistent with either DIP or RBILD in six of eight patients. Although seven patients remained stable or improved, either with or without treatment, three patients deteriorated. CONCLUSIONS: This study adds weight to the hypothesis that smoking can cause clinically significant interstitial lung disease, with deterioration in pulmonary function despite treatment. Given the overlapping histopathological patterns of RBILD and DIP and their strong association with smoking, the term "smoking related interstitial lung disease" is suggested for those patients who are smokers.     

Airway-centered interstitial fibrosis: a distinct form of aggressive diffuse lung disease

We describe 12 patients with a form of interstitial lung disease characterized pathologically by small airway-centered interstitial fibrosis and metaplastic bronchiolar epithelium extending around and often linking fibrotic and sometimes heavily muscularized bronchioles. Clinically, patients presented with chronic cough and progressive dyspnea. One was a current light smoker and two were ex-smokers. In 8 patients, a history of possible inhalational exposures, including wood smoke, birds, cotton, pasture, chalk dust, agrochemical compounds, and cocaine use, was elicited. Pulmonary function tests showed moderate to severe physiologic abnormalities, in most instances indicating a restrictive lung disease with decreased peripheral flow rates. Chest radiographs revealed predominantly diffuse reticulonodular infiltrates in the central lung fields, with thickening of the bronchial walls and decreased lung volumes. Chest computed tomography demonstrated peribronchovascular fibrosis and interstitial thickening. Bronchoalveolar lavage showed a mild increase in lymphocytes in 4 subjects. Patients were treated with corticosteroids and bronchodilators. Follow-up data were available in 10 patients. In 5 patients, the disease progressed and 4 of them died. Two patients remained stable and 3 improved or healed. We propose that these findings represent a distinct airway-centered disease that mostly behaves as an interstitial lung disease and may exhibit a poor outcome.     

Primary lung cancer incidentally diagnosed in lung biopsy for diffuse pulmonary disease

We here presented 2 cases of interstitial pneumonia with lung adenocarcinoma incidentally diagnosed by partially resected lung for diffuse pulmonary disease. CASE 1: A 78-year-old female was admitted to the hospital complaining of productive cough and general fatigue. The chest computed tomography (CT) revealed diffuse honey comb pattern in bilateral lung field especially in the right lower lung. Video-assisted thoracoscopic lung biopsy was performed and was diagnosed as diffuse spreading well differentiated adenocarcinoma. CASE 2: A 59-year-old male was admitted to the hospital complaining of dyspnea and general fatigue. The chest X-ray revealed right pneumothorax and chest CT revealed diffuse honey comb pattern and bullae in bilateral lung field and fibrous tumor-like lesion in the right middle lung. Video-assisted thoracoscopic lung biopsy was performed and was diagnosed as pulmonary fibrosis with papillary adenocarcinoma. CONCLUSION: It is important to examine carefully the specimen obtained from thoracoscopic lung biopsy even if interstitial pneumonia is strongly suspected.     

Diagnostic thoracoscopic lung biopsy: an outpatient experience

BACKGROUND: Tissue diagnosis of either interstitial lung disease or indeterminate pulmonary nodules can be obtained by either limited thoracotomy or thoracoscopic lung biopsy. Both procedures traditionally have required hospital admission. We report a series of patients undergoing outpatient thoracoscopic lung biopsy to demonstrate the safety and efficacy of this practice. METHODS: Sixty-two ambulatory patients with a clinical diagnosis of either interstitial lung disease or indeterminate pulmonary nodule(s) underwent thoracoscopic lung biopsy between June 2000 and June 2001. All procedures were performed with double-lumen endotracheal anesthesia and stapled wedge resection. Chest tubes were removed if no air leak was present and if chest radiograph demonstrated no residual pneumothorax. RESULTS: Of 62 patients undergoing thoracoscopic lung biopsy, 45 (72.5%) were discharged home within 8 hours of observation on the day of operation. Fourteen (22.5%) were discharged within 23 hours of their operation. Reasons for 23-hour observation included significant comorbidity (8), pain management (4), postoperative air leak (1), and conversion to muscle-sparing thoracotomy (1). Three (5%) required admission for prolonged air leak (2) or conversion to muscle-sparing thoracotomy (1). Diagnoses were obtained in 61 patients, including neoplasm (25), interstitial lung disease (18), granulomatous disease (7), and other (11). One patient was readmitted for pneumothorax. Patients diagnosed with nonbronchogenic pulmonary metastases were more likely to be discharged on the day of operation. No differences in age, smoking status, or preoperative pulmonary function testing were observed between patients requiring short-stay observation and those discharged immediately after operation. CONCLUSIONS: Outpatient thoracoscopic lung biopsy is safe and effective, and has become our procedure of choice for diagnosis of either interstitial or focal lung disease.     

Angiotropic large cell lymphoma presenting as interstitial lung disease.

A case of angiotropic large cell lymphoma is reported in which the patient presented with only pulmonary symptoms. It suggests that this rare and highly malignant lymphoma should be considered in the differential diagnosis of interstitial lung disease, and shows the value of open lung biopsy in unexplained interstitial lung disease. This patient responded well to treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone.     

Videothoracoscopy-assisted surgical lung biopsy for interstitial lung diseases

Objectives

Surgical lung biopsy (SLB) by videothoracoscopy for diffuse interstitial lung diseases is recommended for detailed diagnosis. Because substantial mortality and morbidity are associated with this procedure, its safety and diagnostic yield should be validated.

Methods

Sixty-four patients with diffuse interstitial lung disease who received SLB by videothoracoscopy between 2007 and 2013 were retrospectively analyzed for mortality, surgical complication, and diagnosis. Criteria for the procedure included patients <70-year old, who had at least 60 % vital capacity and at least 40 % diffusion capacity. Patients with radiologically definite usual interstitial pneumonia were not eligible.

Results

One conversion from the 3-port approach to thoracotomy due to bleeding occurred. Mean operation and anesthesia times were 63 and 133 min, respectively. The mean hospital stay was 6 days. Only 10 patients (16 %) received prophylactic steroid and/or elastase inhibitor administration. Neither deaths nor acute exacerbations of interstitial pneumonia occurred within 60 days after surgery. Pneumothorax occurred in four cases (6 %) after discharge, which was associated with lower % vital capacity and intraoperative steroid administration. Prolonged air leak and postoperative pneumonia were observed in 2 and 1 patients, respectively. Postoperative diagnosis was obtained in all patients. A group of connective tissue disease-related interstitial pneumonia (n = 15) and chronic hypersensitivity pneumonitis (n = 18) were the major diagnoses. Discordance between pre- and postoperative diagnoses was observed among usual interstitial pneumonia, non-specific interstitial pneumonia, and chronic hypersensitivity pneumonia.

Conclusions

Surgical lung biopsy for diffuse interstitial lung diseases is safe under appropriate inclusion criteria and provides definite diagnosis.     

Peribronchiolar metaplasia: a common histologic lesion in diffuse lung disease and a rare cause of interstitial lung disease: clinicopathologic features of 15 cases

Peribronchiolar metaplasia (PBM) is a histologic lesion consisting of peribronchiolar metaplasia (PBM) of bronchiolar-type epithelium. Although widely recognized, PBM has received little attention in the pathologic literature and is not known to have clinical significance. We identified 15 cases in which PBM was the only major histologic finding in surgical lung biopsies from patients with interstitial lung disease (PBM-ILD), and we reviewed the clinical, imaging, and pathologic findings. The mean age was 57 years (range, 44-74 years) with 13 females and 2 males. One patient had been a welder with fume and asbestos exposure; another had pigeon exposure. Smoking history was available for 13 patients: three current smokers, one cocaine user, two former smokers, and seven never smokers. Three patients had collagen vascular disease. One had elevated serum antinuclear antibody titers. Pulmonary function data were available for 10 patients: one obstructive, five restrictive, two mixed obstructive and restrictive, and two normal. Computerized tomography in 7 patients showed mosaic attenuation in 3 patients and air trapping in 1 patient; no bronchiectasis, septal lines, or honeycombing were seen in any cases. All 11 patients with available follow-up are alive; 4 of them have experienced symptomatic improvement (follow-up, 0.6-6.9 years; mean, 2.4 years). PBM was found focally in other interstitial lung diseases, which were assessed for this lesion: 59% of usual interstitial pneumonia (17 of 29), 50% of nonspecific interstitial pneumonia (10 of 20), desquamative interstitial pneumonia (3 of 6), hypersensitivity pneumonitis (9 of 18), and 11% of respiratory bronchiolitis (2 of 18). In summary, PBM is a common histologic finding in various interstitial lung disorders. It is rarely the sole major lung biopsy finding in patients presenting with interstitial lung disease (PBM-ILD). Patients are mostly older women, with mild symptoms and CT findings. Survival appears to be favorable.     

Regional extravascular density and fractional blood volume of the lung in interstitial disease.

Regional lung density (g lung/ml thoracic volume) and fractional pulmonary blood volume (ml blood/ml thoracic volume) have been measured by positron tomography in 10 patients with interstitial disease. From the measurements regional extravascular lung density (g tissue and interstitial water/ml thoracic volume) was derived, providing a non-invasive measurement of the interstitial reaction. Extravascular lung density was increased and large regional variations were observed. Fractional blood volume was reduced in patients with pulmonary fibrosis. In two patients with sarcoidosis, a reduction in extravascular lung density occurred after treatment with oral prednisone. Abnormalities in extravascular lung density and fractional blood volume correlated with abnormalities shown by tests of overall pulmonary function.     

Diagnostic approach of fibrosing interstitial lung diseases of unknown origin

Interstitial lung diseases encompass a broad range of numerous individual conditions, some of them characterized histologically by fibrosis, especially idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, chronic hypersensitivity pneumonia, interstitial lung disease associated with connective tissue diseases, and unclassifiable interstitial lung disease. The diagnostic approach relies mainly on the clinical evaluation, especially assessment of the patient's demographics, history, smoking habits, occupational or domestic exposures, use of drugs, and on interpretation of high-quality HRCT of the chest. Imaging is key to the initial diagnostic approach, and often can confirm a definite diagnosis, particularly a diagnosis of idiopathic pulmonary fibrosis when showing a pattern of usual interstitial pneumonia in the appropriate context. In other cases, chest HRCT may orientate toward an alternative diagnosis and appropriate investigations to confirm the suspected diagnosis. Autoimmune serology helps diagnosing connective disease. Indications for bronchoalveolar lavage and for lung biopsy progressively become more restrictive, with better considerations for their discriminate value, of the potential risk associated with the procedure, and of the anticipated impact on management. Innovative techniques and genetics are beginning to contribute to diagnosing interstitial lung disease and to be implemented routinely in the clinic. Multidisciplinary discussion, enabling interaction between pulmonologists, chest radiologists, pathologists and often other healthcare providers, allows integration of all information available. It increases the accuracy of diagnosis and prognosis prediction, proposes a first-choice diagnosis, may suggest additional investigations, and often informs the management. The concept of working diagnosis, which can be revised upon additional information being made available especially longitudinal disease behaviour, helps dealing with diagnostic uncertainty inherent to interstitial lung diseases and facilitates management decisions. Above all, the clinical approach and how thoroughly the patient's history and possible exposures are assessed determine the possibility of an accurate diagnosis.     

Phenotypic analysis of alveolar macrophages in normal subjects and in patients with interstitial lung disease.

Cytospin preparations of mononuclear inflammatory cells were made from bronchoalveolar lavage fluid obtained from 15 patients with interstitial lung disease (nine patients with sarcoidosis and six patients with cryptogenic fibrosing alveolitis) and six control subjects. These preparations were examined with a panel of monoclonal antibodies that have been shown to distinguish subpopulations of macrophage like cells in normal tissues. The lysosomal acid phosphatase activity of the cells was also assessed. Phenotypically distinct subpopulations of alveolar macrophages were identified in all samples studied. The results showed that all cell populations identified in bronchoalveolar lavage fluid from the groups with interstitial lung disease could be identified in the lavage fluid from normal volunteers. Some quantitative differences in the proportions of cells identified with particular reagents emerged. In each of the groups with interstitial lung disease increased proportions of cells were identified with RFD1 (interdigitating cell marker; p less than 0.01) and in the cryptogenic fibrosing alveolitis group an increased proportion of alveolar macrophages was identified with RFD7 (tissue macrophage marker; p less than 0.05). The possibility that quantitative changes in alveolar macrophage subsets observed in the interstitial lung disease groups are relevant to the pathogenesis of these conditions is discussed.     

Pulmonary hypertension, interstitial lung fibrosis, and lung iron deposition in thalassaemia major

Although restrictive lung disease is the predominant abnormality of pulmonary function in patients with thalassaemia major (TM), its aetiology and its association with pulmonary hypertension (PH) detected in some patients with TM remains unknown. We report a patient with TM, iron overload, frequent pulmonary infections, and progressive severe precapillary PH over the previous 5 years. A severe restrictive pattern and interstitial lung fibrosis were revealed by pulmonary function tests and high resolution computed tomography, respectively. This presentation suggests that interstitial fibrosis may complicate lung involvement in TM and can significantly contribute to the development of PH.     

Lipoprotein macroaggregates in bronchoalveolar lavage fluid from patients with diffuse interstitial lung disease: comparison with idiopathic alveolar lipoproteinosis.

Lipoprotein macroaggregates were present in cytocentrifuge preparations of bronchoalveolar lavage fluid from four patients with diffuse lung diseases other than idiopathic alveolar lipoproteinosis. In three patients the primary diagnosis was cryptogenic fibrosing alveolitis and in one sarcoidosis. We confirmed the presence of large multilamellar aggregates of lipoprotein by ultrastructural examination in patients with both interstitial lung disease and idiopathic alveolar lipoproteinosis. The small lamellar bodies and amorphous debris found in idiopathic alveolar lipoproteinosis were rare in the patients with interstitial lung disease. The lavage fluid from patient with interstitial lung disease did not show the substantial alterations in phospholipid composition that were seen in lavage fluid in idiopathic alveolar lipoproteinosis. These ultrastructural and biochemical features may help to distinguish idiopathic from other causes of alveolar lipoproteinosis, particularly at an early stage, when differential diagnosis may be difficult.     

Challenges in pulmonary fibrosis . 4: smoking-induced diffuse interstitial lung diseases

Smoking-induced diffuse interstitial lung processes include respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease (RBILD), desquamative interstitial pneumonia (DIP) and Langerhans' cell histiocytosis. The histological, radiological and clinical features of respiratory bronchiolitis, RBILD and DIP are reviewed, with particular reference to management issues; Langerhans' cell histiocytosis is covered elsewhere in this series of articles. Possible relationships between smoking and other diffuse lung diseases are explored briefly.     

Diffuse interstitial lung disease due to AA amyloidosis.

A man developed interstitial lung disease and nephrotic syndrome due to AA amyloidosis. There was no evidence of an underlying disease predisposing to amyloidosis.     

A case of MPO ANCA associated glomerulonephritis with interstitial pneumonitis complicated with lung tuberculosis and pericarditis

The main target organs of myeloperoxidase (MPO) antineutrophil cytoplasmic antibodies (ANCA)-related disease are the kidney and lung. This report describes a 71-year-old man with rapidly progressive glomerulonephritis (RPGN) and interstitial pneumonitis associated with MPO ANCA. The patient was admitted to our hospital because of bloody sputum, low grade fever and appetite loss on October, 1998. He was diagnosed as having interstitial pneumonitis from the findings of chest X-ray and CT examinations. Moderate proteinuria and hematuria, renal dysfunction(serum creatinine: 5.6 mg/dl, BUN: 58.0 mg/dl) and positivity for MPO ANCA were noted. He was negative for anti-glomerular antibody and PR3-ANCA. Renal biopsy was performed and revealed crescentic glomerulonephritis without deposition of immunoglobulins. Therefore, the diagnosis of pauci immune type RPGN was made. Pulse therapy with methylprednisolone(1.0 g/day x 3 days) following oral administration of prednisolone (60 mg/day) found marked improvement of renal function maintenance and interstitial pneumonitis, respectively. However, he died because of lung tuberculosis and acute tuberculous pericarditis during treatment with prednisolone. In this case, MPO ANCA might have been directly associated with both RPGN and interstitial pneumonitis. Furthermore, chronic lung disease, such as interstitial pneumonitis, is important as a preceding disease of RPGN. MPO ANCA-related disease is more frequent in aged persons, therefore particular attention should be paid during their treatment with an immunosuppressant.     

Oxygen desaturation during sleep and exercise in patients with interstitial lung disease.

The relations between mean and maximum fall in arterial oxygen saturation (SaO2) during sleep, hypoxaemia during moderate and maximum exercise, and lung mechanics were studied in 16 patients with interstitial lung disease. Mean and minimum SaO2 during sleep were significantly related to each other and to daytime oxygenation but not to lung mechanics. Although the maximum fall in SaO2 during sleep was similar to the fall during maximum exercise (a level seldom achieved during normal daily activities), profound hypoxaemic episodes during sleep were rare and brief and therefore contributed little to the mean SaO2. The fall in mean SaO2 during sleep was not significant and was considerably less than during moderate exercise (average 0.5 v an estimated 4.5%, p less than 0.05). It is therefore concluded that in patients with interstitial lung disease oxygen desaturation during sleep is mild and less severe than hypoxaemia during exercise.