Endocrinological derangements in COPD.

Chronic obstructive pulmonary disease (COPD) is no longer considered to affect only the lungs and airways but also the rest of the body. The systemic manifestations of COPD include a number of endocrine disorders, such as those involving the pituitary, the thyroid, the gonads, the adrenals and the pancreas. The mechanisms by which COPD alters endocrine function are incompletely understood but likely involve hypoxaemia, hypercapnia, systemic inflammation and glucocorticoid administration. Altered endocrine function can worsen the clinical manifestations of COPD through several mechanisms, including decreased protein anabolism, increased protein catabolism, nonenzymatic glycosylation and activation of the rennin-angiotensin-aldosterone system. Systemic effects of endocrine disorders include abnormalities in control of breathing, decreases in respiratory and limb-muscle mass and function, worsening of respiratory mechanics, impairment of cardiac function and disorders of fluid balance. Research on endocrine manifestations of COPD embraces techniques of molecular biology, integrative physiology and controlled clinical trials. A sound understanding of the various disorders of endocrine function associated with COPD is prudent for every physician who practices pulmonary medicine.

Change of refractive state and eye size in children of birth weight less than 1701 g.

AIMS: To determine the refractive status and ocular dimensions of a cohort of children at age 10-12 years with birth weight below 1701 g, and also the relation between the neonatal ophthalmic findings and subsequent refractive state. METHODS: 293 low birthweight children who had been examined in the neonatal period were assessed at 10-12 years of age. The examination consisted of autorefraction, keratometry, and A-scan. Results of right eyes were compared with published normative data. RESULTS: 293 of the birth cohort of 572 children consented to participate. The average mean spherical equivalent (MSE) in the low birthweight cohort was +0.691 dioptre, significantly higher than the control data (+0.30D, p = 0.02). The average change in MSE over the 10-12 year period was -1.00 dioptre (n = 256), but only 62.1% of cases showed a shift in refractive error of the appropriate magnitude and direction. The presence of any retinopathy of prematurity (ROP) increases the risk of developing anisometropia sixfold. CONCLUSIONS: Low birth weight and ROP both significantly impact the refractive state in the long term. At age 10-12 years children born preterm have an increased prevalence of all refractive errors. In low birthweight children refractive state is relatively stable over the first decade of life with a shift towards myopia of 1 dioptre.

Use of bronchodilator aerosols.

Despite initial fears associated with its safety, aerosol administration by metered dose inhaler (MDI) is rapidly becoming the preferred form of bronchodilator therapy, as it has a number of advantages over oral agents. To enhance aerosol delivery and bronchodilator response, several important steps in the optimal use of an MDI have been characterized. Because many physicians are unaware of the optimal technique in employing an MDI, it is not surprising that patients frequently receive little or no instructions in its use. Furthermore, patients who have received instruction display great difficulty in adhering to the steps in the ideal use of an MDI and frequently cannot coordinate MDI actuation with inspiration. A number of auxiliary delivery systems have recently been developed and show varying success in circumventing the problems involved in patient use of MDIs.

An overview of the pulmonary features of alpha 1-antitrypsin deficiency.

Extensive research, stimulated by the recognition of an association between alpha 1-antitrypsin (alpha 1-AT) deficiency and emphysema, has greatly advanced our understanding of emphysema in general. In this article, we review the literature concerning the basic defect, inheritance, pathogenesis of lung disease, clinical, physiologic, and roentgenographic findings in patients with severe (Pi SZ) deficiency of alpha 1-AT. Data obtained in relatives with alpha 1-AT deficiency, who have not been seen by a physician, should more truly reflect the risk of having lung disease. These studies confirm the increased risk of developing lung disease in cigarette smokers. The implications of the finding that subjects with Pi SZ are probably not at an increased risk of lung disease is discussed with regards to replacement therapy. The natural history of unselected subjects with alpha 1-AT deficiency remains unknown.

Breathing abnormalities during sleep.

The purpose of this communication is to review obstructive and central breathing abnormalities that may occur during sleep, such as obstructive sleep apnea, and Cheyne-Stokes respiration. Emphasis is placed on noninvasive monitoring of the breathing pattern and intrapleural pressure swings by respiratory and surface inductive plethysmography, respectively, which establish the diagnosis of these abnormal breathing patterns.

SR-FTIR Coupled with Principal Component Analysis Shows Evidence for the Cellular Bystander Effect.

Synchrotron radiation-Fourier transform infrared (SR-FTIR) microscopy coupled with multivariate data analysis was used as an independent modality to monitor the cellular bystander effect. Single, living prostate cancer PC-3 cells were irradiated with various numbers of protons, ranging from 50-2,000, with an energy of either 1 or 2 MeV using a proton microprobe. SR-FTIR spectra of cells, fixed after exposure to protons and nonirradiated neighboring cells (bystander cells), were recorded. Spectral differences were observed in both the directly targeted and bystander cells and included changes in the DNA backbone and nucleic bases, along with changes in the protein secondary structure. Principal component analysis (PCA) was used to investigate the variance in the entire data set. The percentage of bystander cells relative to the applied number of protons with two different energies was calculated. Of all the applied quantities, the dose of 400 protons at 2 MeV was found to be the most effective for causing significant macromolecular perturbation in bystander PC-3 cells.

Q fever endocarditis.

Despite a worldwide distribution of Coxiella burnetii, only single cases of Q fever endocarditis have been reported outside Great Britain and Australia. We present 10 patients; five were female, only four had a history of environmental exposure, and the mitral valve was involved as commonly as the aortic stenosis, and three patients had a prosthetic valve. We confirm the importance of hepatic involvement, thrombocytopenia and hypergammaglobulinemia as diagnostic features. Diagnosis was established by finding and elevated complement-fixing antibody to Phase I C. burnetii antigen. Tetracycline, with or without lincomycin or cotrimoxazole, was used in nine patients, and one patient received cotrimoxazole as as the sole antibiotic agent. Optimal duration of therapy is unknown. In one patient, relapse followed when treatment was stopped after 18 months. Valve replacement was necessary in five patients, because of hemodynamic problems. Five patients died, and the means survival is 36 months with a range of five to 66 months. We suggest that Q fever endocarditis is frequently missed, and we recommend clinicians to consider the diagnosis in all cases of culture-negative endocarditis.

Apneustic breathing. A characteristic feature of brainstem compression in achondroplasia?

We have observed apneustic breathing in five patients with achondroplasia. In contrast to experimental models of apneusis, these patients appeared to have intact vagal function and no evidence of pontine disease. However, all our patients displayed clinical, structural, and electrophysiologic features of cervicomedullary compression, a well-recognized complication of achondroplasia. The degree of apneustic breathing was reduced in the majority of our patients following decompressive surgery. Traditional theories on the pathogenesis of apneustic breathing cannot satisfactorily explain the presence of apneustic breathing in our patients. We suggest that cervicomedullary compression may be capable of producing apneustic breathing in the absence of vagal or pneumotaxic center lesions.

Reliability of pulse oximetry in titrating supplemental oxygen therapy in ventilator-dependent patients.

Pulse oximetry is widely used in the critical care setting, but few studies have examined its usefulness in clinical decision making. One area where pulse oximetry might be useful is in the titration of fractional inspired O2 concentration (FIO2) in ventilator-dependent patients. Unfortunately, documented guidelines for this use do not exist, and in a survey of directors of intensive care units, we found that they employed a wide range of target O2 saturation (SpO2) values. Consequently, we undertook a study to determine if SpO2 could be reliably substituted for measurements of arterial O2 tension (PaO2) when adjusting FIO2 in ventilator-dependent patients. We examined a number of SpO2 target values in 54 critically ill patients aiming for a PaO2 of greater than or equal to 60 mm Hg, while minimizing the risk of O2 toxicity. In white patients, we found that a SpO2 target of 92 percent was reliable in predicting a satisfactory level of oxygenation. However, in black patients, such a SpO2 reading was commonly associated with significant hypoxemia (PaO2 as low as 49 mm Hg), and a higher SpO2 target, 95 percent, was required. In addition, inaccurate oximetry readings (ie, greater than 4 percent difference between SpO2 and direct SaO2 measurements) were more common in black (27 percent) than in white patients (11 percent, p less than 0.05). In conclusion, a SpO2 target of 92 percent was reliable when titrating supplemental O2 in white patients receiving mechanical ventilation; however, in black patients, such a SpO2 reading was commonly associated with significant hypoxemia, and a higher SpO2 target, 95 percent, was required to ensure a satisfactory level of oxygenation.

Subjective and objective measurement of cigarette smoke inhalation.

The pattern of cigarette smoke inhalation was studied in 19 smokers with respiratory inductive plethysmography, a reliable unobtrusive ventilatory monitoring device. The mean volumes inhaled varied widely from 0.27 to 1.97 L, with a group mean (+/- SD) of 0.79 +/- 0.45 L. Mean duration of smoke inhalation varied from 2.0 to 6.8 seconds, with a group mean of 4.5 +/- 1.3 seconds. An inhalation fraction was derived by dividing the inhaled volume by the vital capacity; this fraction varied from 0.09 to 0.47, with a group mean of 0.20 +/- 0.10. Subjects rated the depth that they inhaled smoke into their lungs on a visual analog scale and on a grading system. Correlation between visual analog scale and inhalation fraction was poor (r = -0.15). Also, inhalation fraction bore no relationship to smoking pack-years or current pulmonary function. The smokers' inaccurate assessment of their inhalation pattern may help to explain the poor correlation reported between cigarette smoke inhalation and severity of obstructive lung disease.

Modes of mechanical ventilation and weaning. A national survey of Spanish hospitals. The Spanish Lung Failure Collaborative Group.

Little information exists regarding the proportion of patients treated with mechanical ventilation in intensive care units (ICUs), their underlying disease states, the modes of ventilation used, duration of ventilator support, methods and time required for weaning, and mortality in these patients. We carried out a cross-sectional multicenter study in 47 medical-surgical ICUs in Spain to investigate these issues in 290 patients who required mechanical ventilation for at least 24 hs. Relative frequency of different modes was as follows: assist-control ventilation (AC), 55%; synchronized intermittent mandatory ventilation (SIMV), 26%; pressure support ventilation (PSV), 8%; SIMV plus PSV, 8%; pressure-controlled ventilation (PCV), 1%; and continuous positive airway pressure (CPAP), 2%. Overall duration of mechanical ventilation was 27.1 +/- 1.1 (SE). A variety of techniques were used for weaning: T-tube trials, 24%; SIMV, 18%; PSV, 15%; SIMV plus PSV, 9%; and some combination of two or more methods in succession in 33% of the patients. Time required for weaning using a combination of SIMV and PSV was longer (17.8 days) than with other techniques (about 5 days, p < 0.01). Time between initiation of weaning and removal of mechanical ventilation accounted for 41% of total ventilator time and was particularly high (59%) in patients with chronic obstructive pulmonary disease. Overall mortality rate was 34%, and it was higher in patients who were ventilated for 1 to 10 days than in those ventilated for a longer time. Despite the availability of several new modes of ventilator support, older modes such as AC and SIMV were more commonly used. Weaning constitutes a large portion of total ventilator time, and thus, measures that expedite the weaning process should markedly decrease the duration of mechanical ventilation.

Subjective and objective measurement of tidal volume in critically ill patients.

Subjective assessment of the respiratory rate and the adequacy of tidal ventilation are the oldest and most widely practiced forms of respiratory monitoring in critically ill patients. Surprisingly, this method of assessment has itself never been evaluated in patients. The estimation of tidal volume in nine patients was performed by full-time intensive care unit (ICU) personnel and compared to the objective measurement of using a calibrated and validated respiratory inductive plethysmograph (RIP). Linear correlation analysis was performed. Poor correlation between clinical estimation by ICU personnel and actual measurement by RIP was revealed in all cases. A widespread and potentially dangerous tendency to overestimate tidal volume was noted. These data suggest that subjective assessment of tidal volume is inaccurate in critically ill patients and that the development of techniques of continuous, nonobtrusive and objective monitoring are to be encouraged.

Importance of respiratory rate as an indicator of respiratory dysfunction in patients with cystic fibrosis.

Bedside measurement of respiratory frequency is commonly performed in a cursory manner and judged to be of little clinical importance. However, in a recent study of patients being weaned from mechanical ventilation, we found that tachypnea was quite accurate in predicting an unsuccessful weaning outcome. The present study was undertaken to examine the relationship between nonobtrusive measurements of respiratory frequency, using a calibrated inductive plethysmograph, and detailed measurements of pulmonary function in 11 adult patients with cystic fibrosis of varying severity. Respiratory frequency was increased in the patients with cystic fibrosis compared with a group of healthy control subjects, as was minute ventilation and mean inspiratory flow. Respiratory frequency was a sensitive predictor of respiratory dysfunction, being significantly (p less than 0.05) correlated with airway obstruction (r = 0.76), hyperinflation (r = 0.52), arterial oxygenation (r = -0.59), rib cage-abdominal discoordination (r = 0.54), and maximum ventilation during exercise (r = 0.66). Despite the presence of tachypnea, the patients did not display shallow breathing; indeed, tidal volume was not correlated with any of the above abnormalities. In conclusion, respiratory rate was a useful indicator of respiratory dysfunction in this group of patients with cystic fibrosis.

Urine hydrogen peroxide during adult respiratory distress syndrome in patients with and without sepsis.

BACKGROUND: The lung injury in adult respiratory distress syndrome (ARDS) has been associated with increased expiratory hydrogen peroxide (H2O2) concentrations. Furthermore, patients with sepsis and ARDS are reported to have greater serum scavenging of H2O2 than patients with ARDS only. We hypothesized that the systemic presence of H2O2 would be detectable in the urine of these two groups of patients and that, in the case of ARDS sepsis, the relative contribution of each disease to the production this analyte would be discernible. Accordingly, we used an in vitro radioisotope assay to follow the weekly course of urine H2O2 levels in ARDS patients with and without sepsis, and in samples from control non-ARDS patients with sepsis with indwelling urinary catheters and in samples provided by healthy volunteers. METHODS: Thirty patients with ARDS were included in the study: 23 had sepsis and 7 were sepsis free. An indwelling catheter was used to collect urine from each patient over a 24-h period, first within 48 h of ICU admission and then every seventh day over the course of their illness. Urine H2O2 was measured by competitive decarboxylation of 1-14C-alpha-ketoglutaric acid by H2O2. Urine samples were provided by 20 healthy volunteers while, in 10 non-ARDS patients with sepsis, urine was collected over one 24-h period following a 5-day minimum with an indwelling urinary catheter. RESULTS: Urine H2O2 concentration in healthy control subjects (88 +/- 4 mumol/L) and non-ARDS patients with urinary catheters (96 +/- 5 mumol/L) was not significantly different. During the first 48 h in the ICU, urine H2O2 in patients with ARDS only (295 +/- 29 mumol/L) was significantly lower (p < 0.05) than patients with ARDS and sepsis (380 +/- 13 mumol/L); however, the lung injury scores of these two groups did not differ. Furthermore, within the first 48 h, the urine H2O2 of the patients with ARDS and sepsis who did not survive (427 +/- 19 mumol/L; n = 7) was significantly higher than that in patients who survived sepsis (352 +/- 14 mumol/L; n = 15). Thereafter, the lung injury scores and urine H2O2 levels of the nonsurvivor ARDS-sepsis group remained significantly higher compared with the other two groups. At lung injury scores of 3 and 2, regardless of days in ICU, the patients with ARDS only had significantly lower urine H2O2 (266 +/- 30 mumol/L and 167 +/- 24 mumol/L, respectively) compared with the survivor ARDS-sepsis group (376 +/- 19 mumol/L and 250 +/- mumol/L). When the patients with ARDS (both ARDS only and with sepsis) recovered, their urine H2O2 concentration did not differ from the control groups (healthy donors and patients without ARDS). CONCLUSION: Lung injury scores did not differentiate patients with ARDS and sepsis from patients with ARDS only during the first 10 days in the ICU; however, urine H2O2 levels were significantly greater in the patients with ARDS and sepsis. Moreover, despite no initial difference in lung injury, patients who did not survive ARDS and sepsis had consistently greater urine H2O2 concentration than patients who survived sepsis. The urine H2O2 level in the ARDS-only group was about 70 percent of the level in the survivor ARDS and sepsis group, suggesting that ARDS alone is the major contributor to the H2O2 oxidant processes during combined ARDS and sepsis. Furthermore, these studies demonstrate that urine H2O2 may be a useful analyte to differentiate the severity of oxidant processes in patients with ARDS and sepsis albeit the prognosis appears to be survival or nonsurvival.

Validation of respiratory inductive plethysmography in patients with pulmonary disease.

The assumption that the respiratory system behaves with 2 df of motion in healthy persons allows calibration of respiratory inductive plethysmography (RIP) with spirometry (SP). To ascertain whether RIP could be calibrated by the same assumption in patients with lung disease, even though at least 3 df of motion are visualized (ie, upper and lower rib cage and upper and lower abdomen move out of phase), RIP was calibrated by a two-position calibration procedure and validated satisfactorily by simultaneous SP in the erect, semirecumbent, supine, and lateral decubitus positions. In lung disease, the contribution to tidal volume of regions moving independently of the combined rib cage and abdominal movements either is small or remains relatively constant with change of body posture. For clinical monitoring of the resting breathing pattern where patient movements cannot be restricted, respiratory inductive plethysmography can serve as a reliable semiquantitative, noninvasive ventilatory monitoring device.

Aspiration injury due to polyacrylamide.

Acute lung injury secondary to aspiration of polyacrylamide, a synthetic polymer used widely in industry, has not been previously described in man or animal. We report the case of a 26-year-old man who aspirated polyacrylamide gel while cleaning it out of a tank truck. Subsequently, severe airway obstruction and lung parenchymal damage developed, and the patient died. At autopsy, numerous polyacrylamide particles were found in the lungs, along with extensive bronchiolar and alveolar damage.

Long-term prognosis of survivors of Pneumocystis carinii pneumonia. Structural and functional correlates.

Limited data exist detailing the long-term sequelae of Pneumocystis pneumonia. Open lung biopsies were obtained in seven renal transplant recipients within 48 hours of the onset of respiratory failure. Biopsy specimens and simultaneous chest roentgenograms were graded without clinical information according to the severity of alveolar damage and pulmonary infiltrates, respectively. Evaluation of pulmonary function and exercise physiology were performed 15 to 21 months after their illness. Pulmonary function indices were normal except FRC (2.65 +/- 0.56 L or 77 +/- 16 percent of predicted) and Dsb (20.0 +/- 7.2 ml/min/mm Hg or 79 +/- 19 percent of predicted). Two patients developed arterial desaturation with exercise. Alveolar damage scores correlated with later exercise arterial desaturation (r = 0.88, p less than 0.05). Simultaneous roentgenographic scores correlated with later abnormalities of Dsb (r = 0.81, p less than 0.05). Mild residual abnormalities of pulmonary function were found in five of seven adult survivors of Pneumocystis pneumonia. These abnormalities correlated with pathologic and radiographic features of the acute illness.

Breathing patterns. 1. Normal subjects.

Ventilatory monitoring devices that require mouthpiece breathing produce a rise in tidal volume (VT), a fall in frequency (f) and alterations in periodicity and variability of breathing components. Together with the introduction of the respiratory inductive plethysmograph, a reliable noninvasive monitoring device of ventilation, major advances have taken place in understanding the significance of the components of the breathing pattern. We measured the breathing pattern of normal subjects utilizing respiratory inductive plethysmography and continuously processed these data with a microprocessor system. The mean values of the breathing pattern components in normal subjects were not affected by age, but the rhythmicity was more irregular in the elderly. The values of breathing pattern components obtained noninvasively by respiratory inductive plethysmography in normal subjects are fairly predictable in limits similar to other tests of pulmonary function.

Breathing patterns. 2. Diseased subjects.

We measured the breathing pattern of normal subjects, asymptomatic smokers, asymptomatic and symptomatic asthmatic patients, and patients with chronic obstructive pulmonary disease, restrictive lung disease, primary pulmonary hypertension and anxiety state utilizing respiratory inductive plethysmography. Respiratory rate was increased above the normal in smokers and in patients with COPD, restrictive lung disease and pulmonary hypertension, but remained normal in asthmatic patients. Inspiratory times (T1) of one second or less often occurred in patients with COPD, restrictive lung disease, and pulmonary hypertension. Smokers and patients with symptomatic asthma, COPD, restrictive lung disease and pulmonary hypertension showed heightened respiratory center drive as reflected by elevated mean inspiratory flow (VT/TI). Fractional inspiratory time was reduced to a variable extent in smokers, symptomatic asthmatic patients and patients with COPD, and was a weak indicator of airways obstruction. Patients with COPD often had major fluctuations of expiratory timing, periodic fluctuations of end-expiratory level, and asynchrony between rib cage and abdominal movements. Chronic anxiety was characterized by frequent sighs; episodic rapid rates alternating with apneas were less common. We conclude that analysis of breathing patterns provides diagnostic discrimination among normal subjects and disease states.

Separation of factors responsible for change in breathing pattern induced by instrumentation.

Employment of mouthpiece and noseclips (MP + NC) has repeatedly been shown to increase tidal volume (VT), but its effect on respiratory frequency (f) and its subsets is controversial. The mechanisms accounting for this alteration in breathing pattern are poorly understood and may include stimulation of oral or nasal sensory receptors or alteration in the route of breathing. In this study we demonstrated that use of a MP + NC, compared with nonobtrusive measurement with a calibrated respiratory inductive plethysmograph, alters the majority of the volume and time indexes of breathing pattern, with increases in minute ventilation (P less than 0.01), VT (P less than 0.001), inspiratory time (TI, P less than 0.05), expiratory time (TE, P less than 0.05), mean inspiratory flow (P less than 0.05), and mean expiratory flow (P less than 0.05) and a decrease in f(P less than 0.05). Separating the potential mechanisms we found that when the respiratory route was not altered, independent oral stimulation (using an occluded MP) or nasal stimulation (by applying paper clips to the alae nasi) did not change the breathing pattern. In contrast, obligatory oral breathing without additional stimulation of the oral or nasal sensory receptors caused increases in VT (P less than 0.05), TI (P less than 0.05), and TE (P less than 0.01) and a fall in f(P less than 0.05). Heating and humidifying the inspired air did not prevent the alteration in breathing pattern with a MP. Thus change in the respiratory route is the major determinant of the alteration in breathing pattern with a MP + NC.(ABSTRACT TRUNCATED AT 250 WORDS)