A. U. Wells

Variations in histological patterns of interstitial pneumonia between connective tissue disorders and their relationship to prognosis.

Aims and methods:  Pulmonary parenchymal disease is common in patients with connective tissue disorders (CTDs). However, most reports precede recognition of non‐specific interstitial pneumonia (NSIP). We have therefore reviewed 54 lung biopsies from 37 patients with polymyositis/dermatomyositis (PM/DM) (n = 13), Sjögrens syndrome (n = 5), rheumatoid arthritis (n = 17) and systemic lupus erythematosus (SLE) (n = 2) to assess the overall and relative frequencies of patterns of interstitial pneumonia and their impact on prognosis.

Airflow obstruction in bronchiectasis: correlation between computed tomography features and pulmonary function tests

BACKGROUND An obstructive defect is usual in bronchiectasis, but the pathophysiological basis of airflow obstruction remains uncertain. High resolution computed tomographic (CT) scanning now allows quantitation of static morphological abnormalities, as well as dynamic changes shown on expiratory CT scans. The aim of this study was to determine which static and dynamic structural abnormalities on the CT scan are associated with airflow obstruction in bronchiectasis. METHODS The inspiratory and expiratory features on the CT scan of 100 patients with bronchiectasis undergoing concurrent lung function tests were scored semi-quantitatively by three observers. RESULTS On univariate analysis the extent and severity of bronchiectasis, the severity of bronchial wall thickening, and the extent of decreased attenuation on the expiratory CT scan correlated strongly with the severity of airflow obstruction; the closest relationship was seen between decreased forced expiratory volume in one second (FEV1) and the extent of decreased attenuation on the expiratory CT scan (R s = –0.55, p<0.00005). On multivariate analysis bronchial wall thickness and decreased attenuation were consistently the strongest independent determinants of airflow obstruction. The extent of decreased attenuation was positively associated with the severity of bronchial wall thickness, but was not independently linked to gas transfer levels. Endobronchial secretions seen on CT scanning had no functional significance; the severity of bronchial dilatation was negatively associated with airflow obstruction after adjustment for other morphological features. CONCLUSIONS These findings indicate that airflow obstruction in bronchiectasis is primarily linked to evidence of intrinsic disease of small and medium airways on CT scanning and not to bronchiectatic abnormalities in large airways, emphysema, or retained endobronchial secretions.

Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis

In therapeutic studies in idiopathic pulmonary fibrosis (IPF), the low prevalence of significant change in pulmonary functional tests (PFTs) has been a major constraint. The prognostic value of “marginal” changes in PFTs in IPF and fibrotic non-specific interstitial pneumonia (NSIP) was evaluated. In patients with biopsy-proven IPF (n = 84) and NSIP (n = 72), forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DL,CO) trends at 6 months were categorised as “significant” (FVC >10%; DL,CO >15%) or “marginal” (FVC 5–10%; DL,CO 7.5–15%). Proportional hazards analysis and time-dependent receiver operating characteristic methodology were used to examine PFT trends against mortality. In IPF, reductions in FVC were significant in 22 cases (26%) and marginal in 19 cases (23%). Mortality was higher in patients with a significant decline in FVC (hazard ratio (HR) 2.80, 95% CI 1.54–5.06; p<0.001) and those with a marginal decline in FVC (HR 2.31, 95% CI 1.19–4.50; p = 0.01) than in those with stable disease. Progression-free survival was lower when the decline in FVC was marginal than in stable disease (HR 2.34, 95% CI 1.19–4.60; p = 0.01). Marginal changes in DL,CO in IPF and marginal changes in FVC and DL,CO in fibrotic NSIP did not provide useful prognostic information. Marginal change in FVC in IPF denotes a poor outcome. These findings are applicable to clinical practice and to the selection of patients with more progressive disease for therapeutic studies.

High resolution computed tomography as a predictor of lung histology in systemic sclerosis.

BACKGROUND: The relative proportions of fibrosis and inflammation seen by open lung biopsy examination is a predictor of disease outcome in fibrosing alveolitis. This study was designed to assess the ability of high resolution computed tomography to predict the histological appearance of open lung biopsy specimens from patients with systemic sclerosis. METHODS: Twenty abnormal biopsy specimens from 12 patients were assessed; abnormalities were categorised as fibrotic (fibrosis exceeding inflammation) or inflammatory (inflammation equal to or exceeding fibrosis). Computed tomography appearances were scored for the lobe from which the biopsy specimen was taken; scans were graded from parenchymal opacification alone through to a reticular pattern alone. RESULTS: Two lobar appearances were identified on computed tomograms: amorphous parenchymal opacification equal in extent to reticulation (grade 3) and a predominantly reticular pattern (grade 4). There was a significant association between a fibrotic histological appearance and a grade 4 computed tomogram, and between an inflammatory histological appearance and a grade 3 computed tomogram. Computed tomography grade 4 was associated with a fibrotic histological appearance in 12 out of 13 lobes, and grade 3 with an inflammatory histological appearance in four out of seven lobes. CONCLUSION: Computed tomography discriminated between biopsy specimens that were predominantly fibrotic and a smaller group with a larger amount of inflammation.

Desquamative interstitial pneumonia, respiratory bronchiolitis and their relationship to smoking

Aims : Respiratory bronchiolitis (RB) and desquamative interstitial pneumonia (DIP) are closely associated histological patterns of interstitial pneumonia, although there are no studies on the extent of individual histological parameters. Furthermore, the term smoking related‐interstitial lung disease (SR‐ILD) has been proposed as a term to encompass patients with both these histological patterns who give a history of smoking, though it is not well defined how this term relates to historical cases of DIP. The aim of this study was to compare histological parameters in cases of DIP and RB and then to review in detail clinical, imaging and histological data for DIP in relation to a history of smoking.

Accuracy of the typical computed tomographic appearances of fibrosing alveolitis.

BACKGROUND--Open lung biopsy is often performed to confirm the diagnosis in patients with suspected fibrosing alveolitis. The superior sensitivity and specificity of high resolution computed tomography (CT) over chest radiography in various diffuse lung diseases suggest that the characteristic appearance of fibrosing alveolitis on high resolution CT might render biopsy confirmation unnecessary. METHODS--The chest radiographs and high resolution CT scans of 86 patients (41 with fibrosing alveolitis and 45 with various other diffuse lung diseases) were examined individually and independently by two observers. No clinical information was given and the observers gave a level of confidence when the diagnosis was thought to be fibrosing alveolitis. RESULTS--The observers correctly and confidently discriminated between fibrosing alveolitis and other diffuse lung diseases on high resolution CT with an accuracy of 88% and on chest radiography with an accuracy of 76%. The false negative rate for fibrosing alveolitis diminished from 29% on chest radiography to 11% on high resolution CT. The false positive rate on chest radiography was 19% and on high resolution CT 13%; the false positive diagnoses on CT were the result of a few conditions (extrinsic allergic alveolitis, sarcoidosis, cryptogenic organising pneumonia, and pulmonary eosinophilia) which mimicked some of the CT features of fibrosing alveolitis. The superficial similarity of the CT patterns of these conditions are discussed. CONCLUSIONS--High resolution CT is superior to chest radiography in establishing the diagnosis of fibrosing alveolitis and the typical CT appearances are virtually pathognomonic. The diagnostic advantages of CT over chest radiography should further reduce the need for open lung biopsy in this condition.

BAL findings in idiopathic nonspecific interstitial pneumonia and usual interstitial pneumonia.

Idiopathic pulmonary fibrosis (IPF), which has the histological pattern of usual interstitial pneumonia (UIP), is a progressive interstitial lung disease with a poor prognosis. Idiopathic interstitial pneumonias with a histological pattern of nonspecific interstitial pneumonia (NSIP) have a better prognosis than UIP, and may present with a clinical picture identical to IPF. The authors hypothesised that bronchoalveolar lavage (BAL) findings may distinguish between UIP and NSIP, and have prognostic value within disease subgroups. BAL findings were studied retrospectively in 54 patients with histologically proven (surgical biopsy) idiopathic UIP (n=35) or fibrotic NSIP (n=19), all presenting clinically as IPF. These findings were also compared with the BAL profile of patients with other categories of idiopathic interstitial pneumonias. BAL total and differential cell counts did not differ between the two groups. Survival was better in NSIP. In neither group were BAL findings predictive of survival or changes in lung function at 1 yr, even after adjustment for disease severity, smoking andtreatment. BAL differential counts in fibrotic NSIP differed from respiratory bronchiolitis-associated interstitial lung disease, but not from desquamative interstitial pneumonia or cellular NSIP. The authors conclude that bronchoalveolar lavage findings do not discriminate between usual interstitial pneumonia and nonspecific interstitial pneumonia in patients presenting with clinical features of idiopathic pulmonary fibrosis, and have no prognostic value, once the distinction between the two has been made histologically.

The effect of Pseudomonas aeruginosa on pulmonary function in patients with bronchiectasis.

Bronchiectasis patients are susceptible to infection with Pseudomonas aeruginosa. Isolation is associated with increased severity of disease, greater airflow obstruction and poorer quality of life. It is not known whether infection by P. aeruginosa is a marker of disease severity or contributes to disease progression. Consecutive non-cystic fibrosis adult bronchiectasis outpatients (n = 163) with multiple sputum cultures and follow-up pulmonary function tests were designated, according to isolation of P. aeruginosa, as “never infected” (group 1; n = 67), “intermittently isolated” (group 2; n = 82) and “chronically infected” (group 3; n = 14). Based upon change in forced expiratory volume in one second (FEV1) % predicted levels at ≥2 yrs after presentation, longitudinal behaviour was characterised as “improvement” (≥10% rise), “decline” (≥10% fall) or “stability”. Baseline pulmonary-function tests and longitudinal behaviour were examined in relation to pseudomonas status. There was no difference between the groups in age, sex, smoking habit or length of follow-up. Baseline FEV1 levels were highest in group 1 (mean±sd: 77.4±24.3) and higher in group 2 (67.3±25.7) than in group 3 (55.2±18.5). The same significant trends were seen for baseline FEV1/forced vital capacity ratios and diffusing capacity of the lung for carbon monoxide levels. Subsequent longitudinal behaviour was linked to baseline FEV1 levels, which were lowest in patients with improvement and lower in association with decline than with stability. However, longitudinal behaviour did not differ between groups 1, 2 and 3, either before or after adjustment for baseline FEV1 levels. Infection by Pseudomonas aeruginosa occurs in bronchiectasis patients with more severe impairment of pulmonary function but does not influence rate of decline in pulmonary function either before or after adjustment for baseline disease severity. Thus, Pseudomonas aeruginosa is a marker of bronchiectasis severity but is not linked to an accelerated decline in pulmonary function.

Lung function estimates in idiopathic pulmonary fibrosis: the potential for a simple classification

Application of a classification based on simple lung function testing in IPF For many years the idiopathic pulmonary fibrosis (IPF) community has debated the merits of the histopathological classification of idiopathic interstitial pneumonia (IIP).1 The ATS/ERS consensus statement identifies the importance of histological categories of usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). Furthermore, it emphasises that IPF is the clinical correlate of UIP. Despite the recognition of the importance of histological characterisation, surgical biopsy rates vary considerably.2 Most clinicians do not subject their patients to surgical biopsy, despite the potential prognostic benefit of detailed histological evaluation, because many patients are elderly and have significantly impaired lung function and other medical co-morbidities resulting in a potentially high mortality rate.3 In addition, HRCT scanning provides diagnostic data of high sensitivity and specificity for the diagnosis of IPF with acceptable interobserver variability.4,5 Meanwhile, the chronic obstructive pulmonary disease (COPD) and lung transplantation communities have applied simple but pragmatically useful classifications. Bronchiolitis obliterans syndrome (BOS), for example, has been subject to a clinical grading system reflecting the degree of impairment of lung function following lung transplantation. The emergence of a classification based on simple lung function testing occurred because of the difficulties in obtaining adequate tissue for the diagnosis of obliterative bronchiolitis. This is comparable to the situation in IPF where tissue is also difficult to obtain. The success of the classification of BOS is reflected by the publication of an updated version.6 The global initiative for COPD (GOLD) is another example of a consensus classification based on simple lung function testing. GOLD provides a staging system ranging from an “at risk” category to a severe disease category.7 Based on simple lung function testing, it is reproducible and has facilitated the identification of patients with …

A comparison of serial computed tomography and functional change in bronchiectasis

In bronchiectasis the morphological determinants of (marginal) fluctuations in pulmonary function tests are uncertain. The aim of the present study was to evaluate serial computed tomography (CT) changes in relation to pulmonary function trends in patients with bronchiectasis. The relationships between pulmonary function indices and CT scans in 48 adult patients with bronchiectasis were evaluated at baseline and at follow-up, at a median interval of 28 months (range 6–74 months). Two independent observers semiquantitatively scored CT features of bronchial and small airways disease. At initial assessment, the severity of airflow obstruction was linked primarily to the extent of mosaic attenuation. However, serial changes in pulmonary function indices were only associated with serial changes in mucous plugging scores. Alterations in mucous plugging on serial CT were associated with changes in the severity of bronchiectasis and bronchial wall thickness. Greater severity of all three morphological abnormalities at baseline CT were predictive of significant declines in forced expiratory volume in one second, with severe bronchial wall thickness being the most adverse prognostic determinant. Variations in mucous plugging on computed tomography correlate with minor fluctuations in pulmonary function tests in bronchiectasis. However, the severity of bronchial wall thickness is the primary determinant of subsequent major functional decline.