Chris Hilvering

Dead space and slope indices from the expiratory carbon dioxide tension-volume curve

The slope of phase 3 and three noninvasively determined dead space estimates derived from the expiratory carbon dioxide tension (PCO2) versus volume curve, including the Bohr dead space (VD,Bohr), the Fowler dead space (VD,Fowler) and pre-interface expirate (PIE), were investigated in 28 healthy control subjects, 12 asthma and 29 emphysema patients (20 severely obstructed and nine moderately obstructed) with the aim to establish diagnostic value. Because breath volume and frequency are closely related to CO2 elimination, the recording procedures included varying breath volumes in all subjects during self-chosen/natural breathing frequency, and fixed frequencies of 10, 15 and 20 breaths x min(-1) with varying breath volumes only in the healthy controls. From the relationships of the variables with tidal volume (VT), the values at 1 L were estimated to compare the groups. The slopes of phase 3 and VD,Bohr at 1 L VT showed the most significant difference between controls and patients with asthma or emphysema, compared to the other two dead space estimates, and were related to the degree of airways obstruction. Discrimination between no-emphysema (asthma and controls) and emphysema patients was possible on the basis of a plot of intercept and slope of the relationship between VD,Bohr and VT. A combination of both the slope of phase 3 and VD,Bohr of a breath of 1 L was equally discriminating. The influence of fixed frequencies in the controls did not change the results. The conclusion is that Bohr dead space in relation to tidal volume seems to have diagnostic properties separating patients with asthma from patients with emphysema with the same degree of airways obstruction. Equally discriminating was a combination of both phase 3 and Bohr dead space of a breath of 1 L. The different pathophysiological mechanisms in asthma and emphysema leading to airways obstruction are probably responsible for these results.

Expression of the CD11/CD18 cell surface adhesion glycoprotein family and MHC class II antigen on blood monocytes and alveolar macrophages in interstitial lung diseases.

The expression of molecules of the CD 11/CD18 cell surface adhesion glycoprotein family and HLA/DR antigen was studied on peripheral blood monocytes (PBM) and alveolar macrophages (AM) in bronchoalveolar lavage (BAL) fluid from patients with sarcoidosis, idiopathic pulmonary fibrosis (IPF), and extrinsic allergic alveolitis (EAA). Patients with these interstitial lung diseases showed increased numbers of macrophages in BAL fluid. This was probably caused by an increased influx of PBM to the alveoli since the numbers of cells with a monocytic morphology were also significantly increased in BAL samples from patients with interstitial lung disease, most prominently in IPF and EAA.The increased influx of PBM into the alveoli in patients with interstitial lung diseases was not reflected by an increased expression of the CD11/CD18 leukocyte function antigens on PBM.In healthy volunteers as well as in those with sarcoidosis, IPF, and EAA, the percentages of AM positive for CD11b (the C3bi complement receptor) and CD11c were lower than among PBM. This indicates that the expression of these cell surface adhesion molecules is downregulated during maturation and migration of PBM to the alveoli. The absolute numbers of AM positive for CD11b were increased in BAL fluid of IPF and EAA patients compared to healthy volunteers. EAA patients also showed increased absolute numbers of AM positive for CD11a and CD11c. This differentially increased expression of these leukocyte function antigens on AM suggests the influence of locally produced cytokines.

Differences in expression of monocyte/macrophage surface antigens in peripheral blood and bronchoalveolar lavage cells in interstitial lung diseases

The surface antigens of monocytic ceps m oroncnoalveolar lavage (BAL) fluid were analyzed in 10 patients with sarcoidosis, 8 patients with idiopathic pulmonary fibrosis (IPF), 9 patients with extrinsic allergic alveolitis (EAA), and 10 healthy volunteers, and compared with the surface antigens of peripheral blood monocytes (PBM) of the same individuals.The absolute numbers of alveolar macrophages (AM) were increased in all disease groups as were the numbers of small monocyte-like cells, indicating an increased influx of PBM into the alveoli, which was the most prominent in EAA patients.In all groups investigated, the percentages of PBM positive for the monoclonal antibodies (mAb) CD13, CD14, CD33, U26, and Max3 were higher than the percentages of BAL macrophages positive for these markers, while the Max24 marker was equally expressed. In all groups the percentages of AM positive for RFD9 and CD68 were higher than the percentages positive for PBM. The absolute numbers of CD13+ macrophages were increased in IPF and EAA patients, probably due to the increased influx of monocytic cells.The 3 mAb in the CD68 cluster (i.e., Ki-M6, Ki-M7, and Y2/131) demonstrated marked differences in expression on PBM as well as on AM. This is probably because CD68(Ki-M6) recognizes a different epitope than CD68(Ki-M7) and CD68(Y2/131). The latter 2 become increasingly expressed by AM and this is paralleled by an increased CD68(KiM6) expression. The expression of CD68, which is associated with the generation of oxygen radicals during the respiratory burst and increased chemiluminescence, tended to be elevated on PBM and AM of IPF patients, although with a broad range.

Bilateral exudative pleuritis, an unusual pulmonary onset of mixed connective tissue disease.

In mixed connective tissue disease (MCTD) pulmonary involvement has been reported. In most patients diffuse interstitial pulmonary abnormalities are present. We describe an unusual pulmonary onset of MCTD in an 18-year-old woman. She presented with a bilateral pleural exudate containing many granulocytes (95%) and only a few monocytes (5%). High titers of antinuclear antibodies were found. One week after hospitalization, an erythema on both hands and forearms developed. Skin biopsy demonstrated discrete IgM-C3 depositions along the basal membrane of the epidermis, antinuclear antibodies in the nuclei of the keratocytes in the dermis and granular depositions of IgM in the blood vessel walls of the upper dermis. Lung function tests improved without corticosteroid treatment and diffusing capacity remained normal.

Gold-Induced Pneumonitis

Gold-induced pneumonitis is a rare complication of gold salt therapy. We describe a patient with rheumatoid arthritis treated with gold salts, who developed bilateral interstitial pulmonary abnormalities and showed a dramatic response on corticosteroid therapy. Although after 4 weeks of treatment with corticosteroids the chest X-ray and lung function were still abnormal, bronchoalveolar lavage showed a normal cell distribution. Corticosteroid therapy was continued for 8 months since there was still improvement of pulmonary function studies. This case supports the view that in gold-induced pneumonitis a prolonged treatment with corticosteroids may be necessary, as lung function continued to improve.

Does phase 2 of the expiratory PCO2 versus volume curve have diagnostic value in emphysema patients

It has been postulated that serial inhomogeneity of ventilation in the peripheral airways in emphysema is represented by the shape of expiratory carbon dioxide tension versus volume curve. We examined the diagnostic value of this test in patients with various degrees of emphysema. The volumes between 25-50% (V25-50) and 25-75% (V25-75) of the expiratory carbon dioxide tension versus volume curve were determined in 29 emphysematous patients (20 severely obstructed and 9 moderately obstructed), 12 asthma patients in exacerbation of symptoms, and 28 healthy controls. Discriminant analysis was used to examine whether these diagnostic groups could be separated. With regard to phase 2 of the expiratory CO2 versus volume curve (mixture of anatomic deadspace and alveolar air), a plot of intercept versus slope of the relationships of (V25-50) and (V25-75) versus inspiratory volume (VI) from functional residual capacity (FRC), obtained during natural breathing frequency, proved to be most discriminating in the separation between healthy controls and severely obstructed emphysema patients. Separating healthy controls and severely obstructed emphysema patients on the basis of the discriminant line for V25-50, 9 of the 12 asthma patients in exacerbation were classified as normal, and only 5 of the 9 moderately obstructed emphysema patients as emphysematous. For V25-75 involvement of phase 3 of the curve (alveolar plateau) in asthma patients in exacerbation caused a marked overlap with the severely obstructed emphysema patients. In the healthy controls, a fixed breathing frequency of 20 breaths.min-1 led to an increase of both volumes.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucocorticoid receptors in alveolar macrophages: Methodological aspects of the determination of the number of glucocorticoid receptors per cell

Among patients with asthma or chronic obstructive pulmonary diseases the response to glucocorticoids varies considerably. To investigate the possible relationship between clinical response and number of glucocorticoid receptors in alveolar macrophages or theirKD value a micro receptor assay was developed. Assay conditions were adjusted because of receptor occupancy by endogenous or therapeutically used glucocorticoids and high aspecific binding.

Histamine log(dose)-Response Curves in Asthmatics

In 9 asthmatic patients log(dose)-response curves were obtained on 4 successive days with the Wiesbadener Doppelinhalator (WDI) and the De Vilbiss (De V) 645 nebulizer, respectively. log(dose)-respons