No abstract

Eosinophilic inflammation and interleukin-5 (IL-5) expression are characteristic features of the bronchial mucosa in asthma. We have investigated the differential expression of membrane and soluble isoforms of alpha IL-5 receptor (alpha IL-5Rm and alpha IL-5Rs) mRNA in asthmatics and in normal control subjects and examined the correlation between alpha IL-5Rm and alpha IL-5Rs expression and the FEV1 and airway hyperresponsiveness. Nineteen subjects with stable asthma (atopic = 9; intrinsic = 10) and 22 control subjects (atopic = 12; nonatopic = 10) were recruited. Endobronchial biopsies were obtained and processed for in situ hybridization and double-staining techniques. There was a significant increase in the number of cells per millimeter basement membrane expressing mRNA for total, membrane-bound, and soluble alpha IL-5R in asthmatics when compared with that in nonasthmatic control subjects (p < 0.001); 93% of the cells positive for alpha IL-5R mRNA were EG2+ve eosinophils. There was no significant difference in the expression of alpha IL-5Rm and alpha IL-5Rs between the atopic and nonatopic asthmatics. The expression of alpha IL-5Rm and alpha IL-5Rs was also nonsignificantly different between the atopic and nonatopic control subjects. However, in the asthmatic subjects, the number of positive cells expressing mRNA for alpha IL-5Rm inversely correlated with FEV1(r2 = 0.89, p < 0.001), whereas the expression of alpha IL-5Rs mRNA directly correlated with FEV1 (r2 = 0.52, p < 0.001). There were no significant correlations between alpha IL-5R isoforms and the methacholine PC20. These results suggest that alpha IL-5R upregulation and differential regulation of alternatively spliced alpha IL-5R mRNA transcripts may influence the eosinophil response and the accompanying changes in airflow limitation in both atopic and nonatopic variants of chronic asthma.

In eight conscious spontaneously breathing adults we studied the decay of pressure developed by the inspiratory muscles during expiration (PmusI). PmusI was obtained according to the following equation: PmusI(t) = Ers X V(t) - Rrs X V(t), where V is volume and V is flow at any instant t during spontaneous expiration, and Ers and Rrs are, respectively, the passive elastance and resistance of the total respiratory system. Ers was determined with the relaxation method, and resistance with the interrupter method. All subjects showed marked braking of expiratory flow by PmusI. The mean time for PmusI to reduce to 50 and 0% amounted, respectively, to 23 and 79% of expiratory time. During expiration, 24-55% of the elastic energy stored during inspiration was used as resistive work and the remainder (45-76%) as negative work.

The purpose of this study was noninvasive assessment of respiratory compliance and resistance in mechanically ventilated patients with acute respiratory failure (ARF). To this end, flow, change in lung volume, and airway pressure were measured at the proximal tip of the endotracheal tubes in twenty nine critically ill unselected patients. Eleven had acute exacerbation of chronic obstructive pulmonary disease (COPD), 8 had adult respiratory distress syndrome (ARDS) and 10 had ARF of various etiologies. Static compliance (Cst,rs), 'intrinsic' PEEP (PEEPi), as well as minimum and maximum resistance (Rrs,min and Rrs,max, respectively) were obtained with end-inspiratory and end-expiratory airway occlusions. We found that: (1) PEEPi was present in all patients with COPD (up to 11.4 cmH2O) and it was not uncommon in patients with ARF without history of chronic airway disease (up to 4.1 cmH2O). (2) Without correction for PEEPi average Cst,rs was not significantly different between ARDS and COPD patients, whereas the average corrected compliance was significantly lower in ARDS patients. (3) Substantial frequency-dependence of resistance was exhibited not only by COPD patients, but also by ARDS patients.

The forced vital capacity (FVC) maneuver is the most common lung function test. One of its major prerequisites is that it be performed with sufficient effort to achieve the maximal flows that are due to expiratory flow limitation. To verify this, in nine normal subjects, short (0.25-s) pulses of negative pressure (-5 to -20 cmH2O) were applied at the mouth at different times (0.25-1 s) after the onset of 1) FVC maneuvers and 2) vital capacity expirations with submaximal expiratory efforts (SVC). All subjects were experienced in FVC maneuvers. With FVC, the expiratory flow did not change with application and removal of negative-pressure pulses, apart from brief flow transients, mainly reflecting displacement of air from the compliant oral and neck structures. With SVC, flow increased throughout the application of the negative-pressure pulses. Thus application of pulses of negative pressure provides a simple method for on-line recognition of whether an FVC maneuver is performed with sufficient effort to achieve flow limitation.