In most clinical series of patients with cryptogenic fibrosing alveolitis (CFA), disease severity is staged using lung function indices. However, many physiologic indices are measured in routine clinical practice; the choice of variable to evaluate functional severity is contentious. Computed tomography (CT) provides a reproducible means of quantifying the morphologic extent of disease. The aim of this study was to evaluate the functional consequences of smoking-related lung damage in CFA and to identify functional measures best reflecting the extent of fibrosing alveolitis on CT. Sixty-eight patients with CFA were studied. Fourteen patients with emphysema on CT were characterized by relative preservation of FVC and TLC (p < 0.005) and relative depression of DLCO (p < 0.05) and KCO (p < 0.00005). On multivariate analysis, the extent of fibrosing alveolitis and the presence of emphysema were independent determinants of functional impairment; there was no independent relationship between smoking history and functional abnormalities. In patients without emphysema on CT, percent predicted DLCO (r = -0.68), oxygen desaturation on exercise (r = 0.64), and the physiologic component of the clinical-radiographic-physiologic (CRP) score (r = 0.62) correlated much better with the extent of disease on CT than spirometric and plethysmographic volumes. A composite functional index was generated against the extent of disease on CT, using multivariate analysis; comparison with the CRP score suggested that the relationship between morphologic disease extent and the CRP score would be improved by the inclusion of DLCO and by the use of negative weighting for depression of FEV1. These findings indicate that in CFA, the presence of concurrent emphysema on CT has a more profound influence upon functional measures than the smoking history, and underline the importance of both the measurements of DLCO and exercise testing in the assessment of the severity of CFA.

No abstract

This study shows levels of interobserver and intra-observer variation similar to those found in other grading systems in histopathology, with no significant decrease in variability found by abridging the system. The WHO/IASLC system is therefore recommended for future use in both clinical and research fields.

In conclusion, in fibrosing alveolitis of systemic sclerosis, most interstitial Tlymphocytes express the phenotype of memory cells; these cells are likely to be involved in the persistent inflammatory process.

Thin-section computed tomography (CT) provides a reproducible method of quantifying global disease extent and can also discriminate between fibrotic disease, with predominance of reticular abnormalities, and reversible inflammatory cell infiltration, shown as ground-glass attenuation.The aim of this study was to determine whether functional impairment varied according to the presence of ground-glass attenuation on CT, independently of extent of disease on CT, demographic factors, smoking history, therapeutic status, and the type of fibrosing alveolitis (lone cryptogenic fibrosing alveolitis (CFA) versus fibrosing alveolitis associated with systemic sclerosis (FASSc)).Patients with concurrent emphysema on CT (n=16) and FASSc patients with end-stage pulmonary hypertension (n=5) were excluded. One hundred and eleven patients were studied (CFA, n=54; FASSc, n=57).The severity of functional impairment did not vary independently with the presence of predominant ground-glass attenuation, mixed appearance and predominant reticulation on CT. In 34 treated patients undergoing serial CT scanning, the severity of functional impairment did not differ independently between patients with and without regression of ground-glass attenuation at follow-up.We conclude that the severity of functional impairment does not discriminate between inflammatory and fibrotic disease in fibrosing alveolitis, as judged by initial and serial computed tomographic scanning, after adjustment for the morphological extent of disease on computed tomography.

Lone cryptogenic fibrosing alveolitis (CFA) is histologically identical to fibrosing alveolitis associated with systemic sclerosis (FASSc), but it has a much worse prognosis after matching for disease severity at presentation. Thin-section CT scanning (CT) provides a reproducible method of quantifying the morphologic extent of fibrosing alveolitis. The aim of this study was to gain insights into contrasting pathophysiologic mechanisms in the two diseases by comparing patterns of functional impairment after matching for extent of disease on CT, demographic factors, smoking history, and concurrent treatment. Patients with emphysema on CT (n = 16) and patients with FASSc with overt pulmonary hypertension (n = 5) were excluded; 111 patients were studied (CFA, n = 54; FASSc, n = 57). Patients with CFA were distinguished by more severe functional impairment and more extensive disease on CT (40.1 versus 22.1%, p < 0.00005). On multivariate analysis, patients with CFA had greater reduction in arterial P(O2) (p < 0.0005), wider AaP(O2) (p < 0.0005), greater oxygen desaturation on maximal exercise (p < 0.03), and higher dyspnea scores (p < 0.02) than did patients with FASSc after controlling for extent of disease on CT and other covariates. Measures of lung volume and gas transfer did not differ independently between CFA and FASSc. These findings persisted in subanalyses of patients with limited disease, extensive disease, histologic confirmation of fibrosing alveolitis, and with the reinclusion of patients with emphysema and pulmonary hypertension. The patterns of functional impairment were indicative of more severe ventilation-perfusion mismatch or anatomic shunting in CFA after adjustment for disease extent; we speculate that perfusion of poorly ventilated lung parenchyma in CFA occurs through new vessels formed in areas of intense inflammation. This mechanism may contribute to the greater mortality of patients with CFA than of patients with FASSc because of the deleterious effects of hypoxia on concurrent cardiac disease.

Background: Computed tomography (CT) and fine needle guided biopsy (FNB) are often used in the assessment of patients with lung nodules. The influence of these techniques on clinical decision making has not been quantified, especially for small solitary pulmonary nodules (SPN) where the probability of malignancy is lower. A study was undertaken to determine the effect of CT and FNB derived information on clinical decision making in patients with a solitary pulmonary nodule < 3 cm in diameter on initial chest radiography. Methods: Clinical, physiological, and outcome data on 114 patients with an SPN < 3 cm who had subsequent thoracic CT and FNB were extracted from the records of a specialist cardiorespiratory hospital in Auckland, New Zealand. Chest radiographs and CT scans were reported according to specified criteria by a thoracic radiologist. Computer generated summary sheets were used to present cases to each of six clinicians. Each case was presented three times: (1) with clinical data and chest radiograph only; (2) with the addition of the CT report; and (3) with all data including the result of the FNB. Clinicians were asked to specify their management on each occasion and to estimate the probability of the lesion being malignant. Reproducibility was assessed by re-evaluating 24 cases 1 month later. Results: 33 (29%) nodules were benign, 35 (31%) nodules (malignant) were resected with negative node sampling, and 46 (40%) had a non-curative outcome (radiotherapy, incomplete resection, refused therapy). Intra-clinician decision making was consistent for all three levels of clinical data (median κ values 0.79-0.89). Agreement between clinicians on the need for surgery was lowest with chest radiography alone (κ=0.33), rose with CT information (κ=0.44), and increased further with the addition of the FNB data (κ=0.57). The proportion of successful decisions on surgical intervention (against the known outcome) increased with the addition of CT reports and further with FNB reports (p=0.006, Friedman's test). The major benefit of the information added by CT and FNB reports was a reduction in unnecessary surgery, especially when the clinical perception of pre-test probability of malignancy was intermediate (31-70%). FNB data contributed most to the benefit (p<0.001). The addition of CT and FNB was cost efficient and can be applied specifically to patients with a low or intermediate probability of malignancy. Conclusion: Both CT and FNB make cost effective contributions to the clinical management of SPN < 3 cm in diameter by reducing unnecessary operations and increasing agreement between physicians on the need for surgery.

Background: Non-specific interstitial pneumonia (NSIP) and fibrosing alveolitis associated with systemic sclerosis (FASSc) are diseases of unknown aetiology that are characterised by the accumulation of mononuclear cells, followed by the progressive deposition of collagen within the interstitium and subsequent destruction of lung airspace. Better understanding of mediators involved in fibrosis may be useful for early diagnosis and in clinical monitoring of disease progression. Objective: The aim of this study was to investigate the presence of two profibrotic markers, the vitronectin and the endothelin-1 (ET-1) in the airways of NSIP and FASSc patients. Methods: Ten NSIP (6 males, age 57 ± 2 years) and 15 FASSc (8 males, age 55 ± 4 years) patients were recruited along with 10 normal subjects (4 male, age 52 ± 2 years). Vitronectin and ET-1 concentrations were measured in their breath condensate, using a specific enzyme immunoassay. Results: Higher levels of vitronectin and ET-1 were observed in NSIP and FASSc patients [median 92.8 (91.7–93.9) µg/ml; median 8.3 (7.9–9.3) pg/ml] than in control subjects [median 80.3 (89.3–91.4) µg/ml; p < 0.01; median 5.3 (4.9–5.9) pg/ml, p < 0.0001]. We also found increased concentrations of vitronectin in patients with clinical deterioration compared to those remaining stable and in ex-smokers compared to non-smokers and, increased vitronectin and ET-1 in patients treated with steroids compared to untreated patients. Conclusion: These findings justify further studies of vitronectin and ET-1 levels in exhaled breath condensate, as a means of monitoring activity and predicting progression of pulmonary fibrosis.