Chlamydophila (Chlamydia) pneumoniae as a cause of community-acquired pneumonia in Thailand.

Chlamydophila (Chlamydia) pneumoniae infection is increasingly reported worldwide nowadays. We studied twelve Thai adults presenting with the clinical symptoms and signs of community-acquired pneumonia (CAP) due to C. pneumoniae (TWAR) at Pramongkutklao Hospital in Bangkok, Thailand. Their mean age was 38 (range 21-73) years. Six patients lived in Bangkok. Seven patients had comorbid diseases (four cases with allergic asthma, one each with diabetes mellitus, chronic obstructive pulmonary disease and coronary artery disease). C. pneumoniae pneumonia presented as subacute pneumonia in 6 patients. The clinical manifestations were mild (IDSA risk class I-III) except in 4 patients who had preexisting allergic asthma, COPD and coronary heart disease. The diagnosis of C. pneumoniae pneumonia was based on microimmunofluorescence (MIF) antibody technique (IgM titer > or = 1:16, IgG > or = 1:512, IgA > or = 1:256 with or without fourfold rises). The clinical conditions were consistent with the primary infection (IgM titer of 1:16 or higher) in 6 patients and reinfection (IgG titer of 1:512, IgA titer of 1:256 or higher without rises of IgM titer) in the other 6 patients. Minimal bilateral pleural effusion was detected in only one patient. Coinfection was demonstrated in 2 patients (one each with S. pneumoniae and K. pneumoniae). All patients markedly improved after a 2-week course of macrolide, doxycycline or newest fluoroquinolone therapy. All patients had done well at one year of follow-up. C. pneumoniae infection has been recently recognized and a high seroprevalence (37%) in Thai school children and 100 per cent in young male Thai military conscripts has been reported. This report suggests that this infection, C. pneumoniae, may be a common pathogen of CAP in Thailand.

Flow limitation and dyspnoea in healthy supine subjects during methacholine challenge.

The purpose of this study was to assess whether during standard methacholine (Mch) challenge (concentration up to 128 mg x mL(-1)) healthy supine subjects a) develop tidal expiratory flow limitation (FL) and hyperinflation, and b) whether the onset of tidal FL is associated with dyspnoea. Eight healthy subjects were studied. Dyspnoea was assessed using the Borg scale, FL by the negative expiratory pressure (NEP) method and hyperinflation in terms of decrease in inspiratory capacity (IC). Seven patients became flow limited at Mch doses ranging 4-64 mg x mL(-1), with FL encompassing 34-84% of the control tidal volume. In six of them the onset of tidal FL was associated with little or no dyspnoea and a modest degree of hyperinflation (deltaIC <-0.4 L). In one subject, however, onset of FL was associated with a substantial reduction in IC (0.58 L) and moderately severe dyspnoea. In all of these seven subjects FL was transiently reversed after an IC manoeuvre. In conclusion, the results show that a) most healthy subjects may develop flow limitation and hyperinflation during methacholine challenge in supine position, and b) at onset of flow limitation there is little or no dyspnoea, suggesting that onset of dynamic airway compression per se does not elicit significant dyspnoea. Significant dyspnoea probably only occurs with marked dynamic hyperinflation.

Membrane-bound and soluble alpha IL-5 receptor mRNA in the bronchial mucosa of atopic and nonatopic asthmatics.

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.

A simple method to monitor performance of forced vital capacity.

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.

The relationship between airway responsiveness measured before and after the allergen-induced late asthmatic response.

Single blind allergen (Ag) and saline solution bronchial challenges were performed on two successive study days in ten asthmatic subjects. Histamine challenges were performed before, at approximately 2 h (or after resolution of the immediate bronchial response [IR]), and 24 h after saline solution or Ag inhalation. Specific airway conductance (SGaw) was measured after delivery of challenge agents until a 50 percent fall in SGaw was observed. The SGaw was monitored over 8 h for immediate and late asthmatic responses (LAR). Results were expressed as provocative concentrations eliciting a 50 percent decrease in SGaw (SGawPC50HIS). No significant changes from baseline SGaw or SGawPC50HIS were demonstrated after saline solution. Eight subjects (dual reactors) exhibited both an IR and LAR after Ag and two had isolated IRs. Of the eight dual reactors, five had greater than 50 percent decreases in SGawPC50HIS immediately after resolution of the IR and six exhibited such decrements 24 h after Ag provocation. Mean baseline SGawPC50HIS (N = 10) on the Ag challenge day was 3.2 +/- 4.59 mg/ml and decreased to 0.92 +/- 4.56 mg/ml at 102 to 187 minutes after Ag (p = 0.0009) and was significantly decreased from baseline at 1.47 +/- 3.8 mg/ml 24 h after Ag (p = 0.0004). One of the two patients with isolated IR also showed an early onset increase in airway responsiveness (EOR). There was a significant correlation between the percentage of fall from baseline in SGawPC50HIS immediately after the IR and that at 24 h after Ag (r = 0.811, p = 0.005). There was no significant correlation between the decrease in SGawPC50HIS after the IR and the magnitude of the LAR. These data suggest that (1) the early events occurring prior to the LAR may determine changes in airway responsiveness observed at 24 h after Ag challenge, and (2) the EAR to histamine is not exclusively associated with the LAR.

Reproducibility of the vesicular breath sounds in normal subjects.

Nonfiltered (NF) lung sounds from the apical area of the heart along with lung volumes and ECG signals were recorded from 5 normal subjects. The signals were digitized and subjected to three methods of heart sound cancellation: 75-Hz high-pass filtering (75 HF), ECG-triggered blanking (BL) and adaptive noise cancelling (AF) [IEEE Trans. Biomed. Engng 33: 1141-1148, 1986]. The sound signals were then subjected to the fast Fourier transform algorithm to obtain power spectra. Five breaths from each subject were analyzed, and their spectra were similar and slightly skewed to the right. The average values of mean, median and mode frequencies of the whole breath of 5 subjects, respectively, were for NF: 64.62 +/- 3.74, 44.57 +/- 2.06 and 36.75 +/- 1.79 Hz; for 75 HF: 150.42 +/- 17.49, 114.02 +/- 6.43 and 86.16 +/- 3.13 Hz; for BL: 81.76 +/- 6.02, 52.36 +/- 2.79, 41.10 +/- 3.15 Hz; for AF: 96.87 +/- 11.58, 68.23 +/- 10.44 and 52.25 +/- 8.97 Hz. These values showed no differences between subjects. The F values obtained by the two-way analysis of variance of all breaths of all subjects (mean, median, mode) were: NF: 0.161, 0.341, 0.089; 75 HF: 0.455, 0.042, 0.085; BL: 0.108, 0.082, 0.057; AF: 0.130, 0.204, 0.113 (all p greater than 0.1). The data revealed a remarkable lack of variation within and between subjects, suggesting similar sites and mechanisms of production and transmission.

Serial physiologic studies of a chronic obstructive pulmonary disease patient in acute respiratory failure: clues for weaning?

A patient with severe chronic obstructive pulmonary disease was studied during acute respiratory failure. On the day of intubation his respiratory rate was 42, the tidal volume 295 ml, and the maximal inspiratory pressure 8 cm H2O. These parameters improved with rest by mechanical ventilation to 16, 620 ml, and 30 cm H2O, respectively, on the day of successful weaning. Daily tidal volumes correlated significantly with maximal inspiratory muscle pressures (r = 0.936; p less than 0.001). Respiratory system compliances and resistances were measured by the inflation, the end-inspiratory occlusion, and the interrupter methods. In general, inflation compliance and occlusion compliance were comparable and significantly smaller than the interrupter compliance (p less than 0.002 and p less than 0.003, respectively), whereas inflation resistance and occlusion maximal resistance were also comparable but significantly smaller than the interrupter resistance (p less than 0.0008 and p less than 0.0006, respectively). The former was due to increased hysteresis of the pressure volume curves and the latter due to expiratory compression of airways. The compliance was low, and the resistance was high on the day of intubation and became much higher and lower, respectively, on the day of successful extubation. These physiological changes were associated with weaning difficulty. We conclude that respiratory failure and weaning are complex physiologic events under the influence of muscle strength, lung mechanics, gas exchange, and control of breathing. Therefore, prediction of weaning success based upon one or two measured parameters as has been done is probably inadequate in difficult patients.

Adaptive filtering in biological signal processing.

The high dependence of conventional optimal filtering methods on the a priori knowledge of the signal and noise statistics render them ineffective in dealing with signals whose statistics cannot be predetermined accurately. Adaptive filtering methods offer a better alternative, since the a priori knowledge of statistics is less critical, real time processing is possible, and the computations are less expensive for this approach. Adaptive filtering methods compute the filter coefficients "on-line", converging to the optimal values in the least-mean square (LMS) error sense. Adaptive filtering is therefore apt for dealing with the "unknown" statistics situation and has been applied extensively in areas like communication, speech, radar, sonar, seismology, and biological signal processing and analysis for channel equalization, interference and echo canceling, line enhancement, signal detection, system identification, spectral analysis, beamforming, modeling, control, etc. In this review article adaptive filtering in the context of biological signals is reviewed. An intuitive approach to the underlying theory of adaptive filters and its applicability are presented. Applications of the principles in biological signal processing are discussed in a manner that brings out the key ideas involved. Current and potential future directions in adaptive biological signal processing are also discussed.

Inspiratory and expiratory vesicular breath sounds.

Unfiltered breath sounds (NF) from the apical area of the heart, lung volume and ECG signals were recorded in 5 normal subjects. The signals were digitized and subjected to three methods of heart sound cancellation: 75-Hz high-pass filtering (75 HF), ECG-triggered blanking (BL) and adaptive filtering (AF). The sound signals were then subjected to the fast Fourier transform algorithm to obtain power spectra. Inspiratory and expiratory phase sounds of five breaths of each subject were analyzed separately. The inspiratory and expiratory sound power spectra were very similar and skewed slightly to the right, and therefore characterized by median frequencies. The differences between inspiratory and expiratory median frequencies were insignificant for NF: 42.90 +/- 2.03 (mean +/- SD) vs. 46.64 +/- 2.53 Hz (p greater than 0.1); for 75 HF: 106.43 +/- 10.27 vs. 118.22 +/- 6.30 Hz (p greater than 0.5); for BL: 44.46 +/- 3.33 vs. 66.73 +/- 2.93 Hz (p greater than 0.1), for AF: 49.72 +/- 5.68 vs. 79.20 +/- 13.07 Hz (p greater than 0.1). We conclude that the lack of significant differences suggests similar mechanisms and sites of production of inspiratory and expiratory vesicular breath sounds.

Autoregressive modeling of lung sounds: characterization of source and transmission.

In this communication, we discuss the application of autoregressive modeling to lung sounds analysis. The lung sounds source in the airway is modeled as a white noise source, consisting of one or a combination of the following sources: random white noise sequence, periodic train of impulses, and impulsive bursts of energy. The acoustic transmission through the lung parenchyma and chest wall is modeled as an all-pole filter. Using this method, the source and transmission characteristics of lung sounds are estimated separately, based on the lung sounds at the chest wall. To illustrate the potential validity of the model, lung sound segments in known disease conditions were selected from teaching tapes and the source and transmission characteristics were estimated by applying the model. The estimated characteristics were found to be consistent with current knowledge of the generation and transmission of lung sounds in the known conditions.

Early detection of pulmonary congestion and edema in dogs by using lung sounds.

Five mongrel dogs (2 interstitial and 3 alveolar edema) were studied. Lung mechanics were measured by recording the flow, volume, and esophageal pressure according to the standard technique. Edema was produced by infusion of Ringer lactate solution. Lung sounds were recorded on tape from the dependent part of the chest wall. Lung sound signals were high-pass filtered at 100 Hz and subjected to fast Fourier transform. Samples of lung sounds were analyzed before (control) and at 5, 10, 20, 30, and 40 min after the infusion. The mean, median, and mode frequencies of sound power spectra at the control time were, respectively, 169.6 +/- 29.19, 129.6 +/- 29.81, and 136.0 +/- 29.87 (SD) Hz. These values increased significantly at 5 min after infusion to 194.0 +/- 26.08 (P less than 0.0037), 150.2 +/- 23.48 (P less than 0.0085), and 164.6 +/- 28.74 Hz (P less than 0.02), respectively. These values stayed significantly elevated at 10, 20, 30, and 40 min. The pulmonary wedge pressure, lung dynamic compliance, and pulmonary resistance were measured also at the same times. The mean, median, and mode frequencies correlated with pulmonary wedge pressure (P less than 0.00001, P less than 0.0001, P less than 0.0001), lung dynamic compliance (P less than 0.001, P less than 0.0001, P less than 0.0001), and pulmonary resistance (P less than 0.00001, P less than 0.00001, P less than 0.0001), respectively. There were no significant adventitious sounds up to 40 and 50 min after infusion. We concluded that pulmonary congestion and early edema alter the frequency characteristics of lung sounds early, before the occurrence of adventitious sounds. These altered lung sounds may be used as an index of pulmonary congestion and impending edema.

Characteristics of normal lung sounds after adaptive filtering.

Lung sounds were recorded from five normal male subjects during tidal breathing. Simultaneous electrocardiograms were recorded and used as index signals to generate simulated heart sounds for digital subtraction from recorded lung sounds to obtain purer lung sounds. Five random breaths from each subject were analyzed. Sound signals were band-pass filtered 25 to 1,000 Hz (antialiasing), digitized at 3,000 Hz, and then subjected to (1) direct fast Fourier transform (FFT) without filtering (NF); (2) digital high-pass filtering at 75 Hz and subsequent FFT (75 HzF); (3) adaptive filtering and subsequent FFT (AF). The FFT algorithms of all lung sounds were characterized by mean, median, and mode frequencies. The mean, median, and mode of NF were lower than those of 75 HzF (64.98 +/- 4.04 versus 150.42 +/- 17.49, mean +/- SE, p less than 0.003; 44.57 +/- 2.06 versus 111.81.5.78, p less than 0.0003; 36.81 +/- 1.77 versus 86.16 +/- 3.13, p less than 0.0001) and those of AF (64.98 +/- 4.04 versus 96.87 +/- 11.58, p less than 0.01; 44.57 +/- 2.06 versus 68.23 +/- 10.44, p less than 0.05; 36.81 +/- 1.78 versus 52.24 +/- 8.97, p less than 0.06). The mean, median, and mode of AF were lower than those of 75 HzF (96.87 +/- 11.58 versus 150.42 +/- 17.49, p less than 0.02; 68.23 +/- 10.44 versus 111.81 +/- 5.77, p less than 0.007; 52.24 +/- 8.97 versus 86.16 +/- 3.73, p less than 0.01). The results indicated that by filtering out low frequency heart sounds, the frequency spectrum of lung sounds was moved upward.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantification of heart sounds interference with lung sounds.

An index to quantify the contamination of lung sounds by heart sounds is described. Using the index, the efficacy of high pass filtering and adaptive filtering methods for the reduction of heart sounds is evaluated.

Pressure flow characteristics of commonly used heat-moisture exchangers.

Heat-moisture exchangers or "artificial noses" are commonly used to humidify the inspired air in intubated or tracheostomized patients. These devices add resistance to breathing that may be significant in critically ill and weak patients, especially when the devices are humidified. Three of each six commonly used types (Portex, SH 150, SH 151, NCC, Engström, and PaII) were tested to define the pressure flow characteristics. Known flows were passed through these devices, and the pressure drops across them were measured. The devices were tested when they were dry and when they were humidified with 100% saturated water vapor for 8, 16, and 24 h. The amount of water added to the devices was measured. The pressure flow characteristics of the devices could be described by a power function: P = aVb, where P is pressure, V is flow, and a and b are constants determined by the characteristics of the devices. In addition, the resistance increased with the increasing weight of the devices from added moisture clogging the pores of the felt pads contained inside.

Airflow and normal lung sounds.

The relationship between total air flow and normal breath sounds recorded at 2 sites on the chest was investigated. Sounds were measured during rhythmic breathing, during flow rate tracking, and during flow rate tracking against an external resistance by subjects seated and in the left lateral decubitus position. The sound amplitude during inspiration varied directly with the square of the air flow at the mouth. Changes in subject position and breathing pattern altered the gain between the square of the flow and the sound amplitude but not the functional relationship.

Factors influencing the production of wheezes during expiratory maneuvers in normal subjects.

We recorded wheezes, pleural pressure, plethysmographic lung volumes and mouth flow rates in 6 healthy subjects during maximal expiratory maneuvers breathing air and a mixture of 80% He-20% O2 (He) before and after methacholine inhalation. During expiratory flow maneuvers a critical pleural pressure was needed before wheezes occurred. All but one wheeze occurred in the last two thirds of vital capacity during forced exhalation where flow limitation existed. At a flow rate of 2 liters/s, the critical pleural pressure breathing air was 21 +/- 5.8 cm H2O (mean +/- SD), whereas that of breathing He was higher: 32 +/- 7.8 cm H2O (p less than 0.02). In addition the wheezes occurred at lower lung volumes (associated with small airway diameters) when He was breathed instead of air. This was seen both before (p less than 0.02) and after (p less than 0.01) methacholine. These findings suggested that for a given flow rate a lighter gas such as He had to acquire a higher linear velocity so that the convective acceleration was sufficient to produce wheezes. This was achieved by either an increase in the driving critical pleural pressure or narrowing of bronchi by a larger compressing pleural pressure or smaller lung volumes.

Respiratory compliance and resistance in mechanically ventilated patients with acute respiratory failure.

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.

Respiratory mechanics in the adult respiratory distress syndrome.

Recent methods developed for noninvasive determination of the mechanical properties of the respiratory system have been discussed. These methods have already provided valuable information in patients mechanically ventilated in the ICU setting, and could readily be applied to ARDS. More extensive use of such methods should help to provide a better understanding of the physiologic processes and adaptive mechanisms present in both health and disease.

The pathophysiology and response to steroid therapy in sarcoidosis.

Fourteen patients with early sarcoidosis were prospectively studied over a period of 12-24 months. After baseline physiologic measurements they were treated with 40 mg of prednisone daily for 8 weeks and the measurements were repeated. Thereafter, the steroid dosage was reduced to 0-10 mg every other day and the measurements were repeated between the 12th and 24th month. Relatively normal lung volumes (VC, FRC, RV, TLC) and low DLCO increased with 8-week intensive steroid treatment and fell to below the pretreatment levels when the steroid was either tapered or stopped. The Vmax50-air, Vmax50-He, FEF25-75, upstream conductance (Gus) increased during intensive treatment whereas the RL fell and the FEV1/FVC ratio did not change. The CC/TLC, CV/VC, delta N2, CLdyn/CLst, delta Vmax50 were abnormal in many patients and did not change after 8 weeks of steroid treatment. We concluded that the obstructive defect is common in early sarcoidosis, predominantly in small airways and patchy in nature; the functional derangement is always improved by intensive and adequate steroid therapy and worsened when the drug is tapered or stopped.