Predictors of functioning of patients with chronic obstructive pulmonary disease.

OBJECTIVE: To determine the extent to which mood, symptoms, lung function, and social support of patients with chronic obstructive pulmonary disease (COPD) predicted their level of functioning over a 30-month period. DESIGN: Prospective, longitudinal. SETTING: The homes of patients living in or adjacent to metropolitan Toronto. SUBJECTS: Seventy-one patients (48 men and 23 women) with COPD who had a forced expiratory volume in 1 second less than 50% of predicted (FEV1 < 50%) and who spoke English. They ranged in age from 43 to 81 years (mean 66.37 years). OUTCOME MEASURES: The patients' level of functioning at the final data collection visit, 30 months after the initial measure. INSTRUMENTS: At both data collection visits patients completed measures of mood (negative mood scales of the Profile of Mood States), symptoms (Bronchitis-Emphysema Symptom Checklist), social support (Personal Resource Questionnaire), and functioning (Sickness Impact Profile). RESULTS: Data were analyzed by use of multiple regression analysis. From measures taken at the initial visit (T1), the best predictors of patients' functioning at 30 months (T2) were their functioning at T1, symptoms, FEV1, and age. Together these accounted for 70% of the variance in the final functioning scores, with initial functioning scores accounting for 51% of the variance. The most prevalent symptoms were dyspnea and fatigue, and both were highly correlated with functioning scores 30 months later. CONCLUSIONS: In this study, symptoms, FEV1, and age are predictive of functioning in patients with COPD over a 30-month time frame. However, only 50% of the 143 patients recruited into the study completed it. Therefore caution needs to be exercised when the results are applied to other patients with COPD.

Mask lung ventilation by ambulance personnel: a performance assessment.

We evaluated the ability of basic life support ambulance officers and anaesthetists to perform lung ventilation with a face mask. After induction of anaesthesia and institution of standardized airway conditions the ambulance officer or anaesthetist placed a mask on the patient's face and lung ventilation was commenced. The order of hand grip (one vs two hands) was randomized. The mask was connected to a ventilator which had flow and pressure transducers in the inspiratory and expiratory breathing circuits. The output of these devices was sent to an electronic integrator to determine volumes. Calibration of the flow transducers was made against a spirometer while ventilating a test lung. Oesophageal insufflation was determined by listening over the epigastrium with a stethoscope. Data collected included presence of gastro-oesophageal insufflation, inspiratory and expiratory volumes. Expiratory volumes for ambulance officers and anaesthetists at 30 cm H2O were greater than that of ambulance officers at 20 cm H2O (P < 0.001) but profession of the mask holder or hand grip had no effect on expiratory volume. There was no difference in the mask leak when the professions were compared but ambulance officers had a lower mask leak with a two-handed grip at 20 cm H2O (P < 0.001). Anaesthetists had a greater incidence of gastro-oesophageal insufflation when a two-handed mask grip was utilized (P < 0.05). In healthy relaxed patients there appeared to be little difference between the ambulance officers and qualified anaesthetists in airway maintenance or mask-holding ability.

Bioequivalence of two methotrexate formulations in psoriatic and cancer patients.

OBJECTIVE: To compare the bioequivalence of a generic methotrexate (MTX) tablet (Mylan) with that of a brand-name (Lederle) product. DESIGN: A single-dose, randomized, crossover study. SETTING: Clinical Research Center (CRC) at a university hospital. PATIENTS: Men and women who had a diagnosis of malignancy or psoriasis who were at least 21 years old. METHODOLOGY: Two overnight study periods were scheduled at the CRC at least one week, but not more than two weeks apart. Each period consisted of a 10-hour fast prior to and 4 hours following oral MTX 15 mg administered as six 2.5-mg tablets. Blood samples were collected over 48 hours. Plasma MTX concentrations were determined using an HPLC assay. Area under the curve from zero to infinity (AUC0-infinity) was calculated by the log-trapezoidal method. RESULTS: Twenty-two patients (21 psoriasis, 1 colon cancer) aged 23-61 years completed both study periods. Mean values for peak concentration, time to peak concentration, and AUC0-infinity were 0.80 mumol/L, 1.2 hours, and 3.0 mumol.h/L, respectively, for Mylan's MTX tablets and 0.81 mumol/L, 1.4 hours, 3.0 mumol.h/L, respectively, for Lederle's MTX. Normalization for weight or body surface area did not affect interpatient variability. Relative bioavailability of generic MTX was 99.2 percent. Rate and extent of absorption were not significantly different and the confidence intervals were within the range of 80-120 percent required by the Food and Drug Administration. CONCLUSIONS: Mylan's MTX tablet is bioequivalent to Lederle's product.

Surgeons' reported attitudes and practices regarding alaryngeal speech.

Attitudes and practices of 50 prominent laryngologic surgeons were surveyed to determine current trends and implications for postoperative speech rehabilitation. Data are available for 1,003 laryngectomy operations performed over the past 3-year period by the 22 responders (44%). Those surgeons responding indicated a preference toward tracheoesophageal shunt procedures. A negative correlation was noted between the increased number of tracheoesophageal shunt procedures and the age of the surgeon. Additional responses provided information regarding personal preferences for postlaryngectomy speech types, opinions regarding artificial device use, and speech rehabilitation referral practices.

Changes in tracheal cross-sectional area during Mueller and Valsalva maneuvers in humans.

Pressure-area behavior of the excised trachea is well documented, but little is known of tracheal compliance in vivo. Extratracheal tissue pressures are not directly measurable, but transmural pressure for the intrathoracic trachea is inferred from intra-airway and pleural pressure differences. Extramural pressure of the cervical trachea is assumed to be atmospheric. The difference in transmural pressure between the intra- and extrathoracic tracheal segments should be exaggerated during Mueller and Valsalva maneuvers. We used the acoustic reflection technique to measure tracheal areas above and below the thoracic inlet during these isovolume-pressure maneuvers. We found that 10 cmH2O positive pressure increased tracheal area in the extrathoracic segment by 34 +/- 16% (mean +/- SD) and in the intrathoracic segment by 35 +/- 15%. There was a reduction in area of 27 +/- 16 and 24 +/- 14%, respectively, for the extra- and intrathoracic segments with 10 cmH2O negative pressure. We conclude that the effective transmural pressure gradients do not vary significantly between intra- and extrathoracic tracheal segments.

Lung volume dependence of esophageal pressure in the neck.

There is conflicting evidence in the literature regarding tissue pressure in the neck. We studied esophageal pressure along cervical and intrathoracic esophageal segments in six healthy men to determine extramural pressure for the cervical and intrathoracic airways. A balloon catheter system with a 1.5-cm-long balloon was used to measure intraesophageal pressures. It was positioned at 2-cm intervals, starting 10 cm above the cardiac sphincter and ending at the cricopharyngeal sphincter. We found that esophageal pressures became more negative as the balloon catheter moved from intrathoracic to cervical segments, until the level of the cricopharyngeal sphincter was reached. At total lung capacity, esophageal pressures were -10.5 +/- 2.9 (SE) cmH2O in the lower esophagus, -18.9 +/- 3.0 just within the thorax, and -21.3 +/- 2.73 within 2 cm of the cricopharyngeal sphincter. The variation in mouth minus esophageal pressure with lung volume was similar in cervical and thoracic segments. We conclude that the subatmospheric tissue pressure applied to the posterior membrane of the cervical trachea results in part from transmission of apical pleural pressure into the neck. Transmural pressure for cervical and thoracic tracheal segments is therefore similar.

Wall motion in expiratory flow limitation: choke and flutter.

Limitation of expiratory airflow from mammalian airways is currently understood to be due to choking at wave speed (S. V. Dawson and E. A. Elliott. J. Appl. Physiol. 43: 498-515, 1977). A critical weakness of the theory is the lack of a mechanism for the dissipation of energy when effort exceeds that needed for maximal flow. We have observed substantial wall motion with flow limitation in a physical model of a trachea. Therefore we have examined a simple two-dimensional mathematical model, designed to approximate the behavior of the physical model of the trachea, to try to identify a relationship between flow limitation and wall oscillation. The model matches wave-speed predictions when only long waves are considered. The model predicts that aerodynamic flutter will occur in the zone of supercritical flow described in wave-speed theory. Aerodynamic flutter in the zone of supercritical flow provides a potential mechanism for the energy dissipation necessary for transition from supercritical to subcritical flow and explains the high-frequency pure tone heard with flow limitation.

Improved expiratory airflow dynamics with smoking cessation.

Lung recoil, Pst(1), dependence and gas density dependence of maximum expiratory flow (Vmax) using air and an 80% helium + 20% oxygen (HeO2) gas mixture before and 60 +/- 4 (means +/- SD) days after cessation of smoking were determined in five male and five female subjects (33.4 +/- 6.4 years). Pst(1) dependence of Vmax, a relationship dependent on airway elastance at the "choke", was estimated by measuring the slope and the zero flow intercept using the maximum flow-static recoil (MFSR) curve. MFSR slope was unchanged by abstinence. The intercept showed no difference between air and HeO2 before or after cessation of smoking. Density independence of the zero flow intercept is deducible from wave speed theory if there is no change at the "choke" and the slope truly reflects the elastic behaviour of the "choke". This correspondence of theory and measurement suggests that the "choke" was not changed by abstinence. The reduction of Pst(1) with smoking cessation, without any fall in Vmax at the same lung volume, suggests a complementary reduction in lung recoil and frictional energy loss upstream of the "choke". This would suggest that a decrease in small airway muscle tone was the single cause of a reduction of Pst(1) and peripheral airway resistance.

Lung recoil during rapid vital capacity expirations simulated by gas compression.

Excised dog lobes were inflated to a transpulmonary pressure (PL) of about 30 cmH2O, and their airways were occluded. Then they were rapidly compressed to a volume where PL was about zero, simulating forced expiratory maneuvers. Since there was no airflow during the compression, PL was a direct measure of lung recoil. Lung volume (VL) was calculated from absolute airway pressure using Boyle's law. At ambient temperature, lung recoil pressure during compressive maneuvers simulating forced vital capacity expirations (Pdyn) was less than that during quasi-static (30 s) compressions (Pst). Typically the dynamic component (i.e., Pst--Pdyn) decreased from about 2 cmH2O near total lung capacity to no difference at the end of the compression. Cooling the lobes to 15 degrees C increased Pst-Pdyn, and warming the lobes to 37 degrees C reduced Pst-Pdyn almost to zero. We suggest that the driving force of lung recoil during expirations is adequately modeled by the quasi-static VL/PL relationship, though a small correction should be made for excised lungs at room temperature.

Pulmonary function in identical twins: comparison of nonsmokers and smokers.

Forty-five apparently normal pairs of identical twins were given pulmonary function tests to determine the role of genetics in bronchial susceptibility to cigarette smoke. Maximal expiratory flow at 60 per cent of total lung capacity (Vmax60) was the best discriminator of smokers from nonsmokers among pairs in which one member smoked and the other did not. The intrapair difference of Vmax60 values in pairs in which both members smoked was the same as in pairs in which both members did not smoke. These data support the view that genetic factors are important in determining the vulnerability of the airways to cigarette smoke.

Volume dependence of instantaneous time constants derived from the maximal expiratory flow-volume curve. A new approach to the analysis of forced expiration.

A simple expansion of the information in the maximal expiratory flow-volume curve was used to measure the convexity to the volume axis of maximal expiratory flow-volume curves produced by 11 asymptomatic smokers and 11 asymptomatic nonsmokers. The ratio of remaining volume to maximal flow was equal to the product of upstream resistance and chord compliance. This "instantaneous time constant" increased more near residual volume in the smokers. Using this method, plethysmographically obtained maximal expiratory flow-volume curves were more sensitive than spirometrically obtained maximal expiratory flow-volume curves. This method compared favorably with moment analysis and helium response of maximal expiratory flow as a separator of asymptomatic smokers and nonsmokers.