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The present study sought to measure the accuracy of symptom reporting in patients with asthma by calculating the difference between a subjective rating of illness severity and an objective test of lung function (forced expiratory volume in 1 second). At issue was the hypothesis that self-reported "symptom amplification" or sensory awareness accounts for differences in the accuracy of symptom reporting. Spirometric examination was performed, and psychological tests of symptom amplification, emotional distress, and neuroticism were administered. Participants consisted of 42 consecutive patients seeking medical treatment of asthma. The disparity between symptom perception (assessed by a Borg scale) and a corresponding measure of lung capacity allowed us to identify patients who overreported their symptoms (amplifiers) along with those who underreported them (minimizers). After controlling for the effects of sex and psychological distress, a self-report measure of symptom amplification explained 15% of the variability in reporting accuracy. Related constructs such as somatization and neuroticism could not explain differences in reporting ability.

Objectives: To test the hypothesis that patients with well-documented diastolic dysfunction (DD) in the setting of normal systolic function will have inspiratory muscle weakness when compared to normal control subjects, and will experience dyspnea and tachypnea during exercise. Background: Respiratory muscle weakness has been described in patients with (systolic) congestive heart failure; however, whether or not patients with DD may present with the findings of congestive heart failure is not known. Methods: We selected for study 14 patients with DD previously referred for cardiopulmonary evaluation whose diagnosis had been confirmed by data obtained at cardiac catheterization. Seven control subjects matched for age, sex, and weight were recruited from the hospital community. Subjects performed both basic pulmonary function tests and tests of muscle strength: handgrip strength (Hgr), and maximal subatmospheric static inspiratory muscle pressure (P i max). Subjects then performed a graded exercise test on a bicycle ergometer. Minute ventilation, oxygen consumption, carbon dioxide production, and heart rate were monitored continuously. Echocardiography was performed three times: before exercise, at a selected submaximal exercise level (20% of a predicted maximal workload), and at maximal exercise. Subjects rated their degree of dyspnea using the Borg scale at the same three time intervals. Results: P i max was − 102 ± 17 cm H 2 O in control subjects, and − 77 ± 19 cm H 2 O in patients with DD (p = 0.013) [mean ± SD]. Hgr was similar between the groups. At the selected submaximal exercise level, patients with DD rated dyspnea to be 2.6 ± 2.2 Borg scale units (control subjects, 0.5 ± 0.8 Borg scale units). Hey plots described a rapid, shallow breathing pattern in patients with DD during exercise. Patients with DD and control subjects achieved similar maximal work loads. Conclusion: Patients with DD have diminished P i max, adopt a rapid, shallow breathing pattern during exercise, and experience dyspnea at low work loads when compared to matched control subjects.

Background: Airway function, as assessed by standard spirometry, and the intensity of dyspnea reported by asthmatic patients correlate poorly. Objective: This study tests the following two hypotheses: (1) that measures of the tendency of a patient to somatize will reduce the variation in the report of dyspnea not explained by airway function; and (2) that plethysmography is a better tool with which to estimate the degree of dyspnea associated with asthma. Design: A prospective laboratory study carried out over one study session. Participants: Forty asthmatic subjects who had withheld bronchodilator (BD) therapy overnight. Interventions: We performed spirometry, plethysmography, and an assessment of dyspnea (ie, modified Borg scale) on all subjects before and after they received BD therapy. Standard questionnaires pertaining to psychological state and trait were administered as well. Results: The change in specific airway conductance with BD therapy correlated with a decline in the Borg score (r 5 0.47; p 5 0.007). By contrast, neither spirographic measures nor measures of static lung volumes correlated. Correlation with the Borg scale score was not improved by adding indexes of either somatization or psychological state or trait. Conclusion: The relief of dyspnea reported by patients with mild asthma after BD therapy is related to dilatation of the central airways. (CHEST 2001; 120:409 ‐ 415)

Objective: To evaluate the natural history of chronic fatigue syndrome (CFS) in a severely ill group of patients at three points in time. Design: Patients were enrolled from April 1992 to February 1994 and were evaluated three times. Time 1 (at enrollment): history, physical evaluation, and psychiatric evaluation; Time 2 (median = 1.6yrs after initial evaluation): postal questionnaire to assess current condition; Time 3 (median = 1.8yrs after Time 2): medical and psychiatric evaluations. Setting: The New Jersey CFS Cooperative Research Center, an ambulatory setting. Patients: Twenty-three patients fulfilled the 1988 case definition for CFS and had symptom complaints that were substantial or worse in severity. All patients were ill less than 4.5 years; and none had a DSM-III-R psychiatric disorder in the 5 years before illness onset; none had substance abuse in the 10 years before enrollment. Main Outcome Measures: Severity of CFS symptoms was assessed by self-report questionnaires, laboratory tests, and medical examination. Psychological status was assessed using the Q-D15 and the Centers for Epidemiological Study—Depression Scale. At each time of evaluation, patients were categorized as severe, slightly improved, improved, and recovered. Results: Over the 4 years of the study, 13 patients remained severely ill, 9 improved but still fulfilled the 1994 case definition for CFS, and 1 recovered. Illness duration, mode of onset, psychiatric status or depressed mood at intake, or chemical sensitivity did not predict illness outcome. One patient was diagnosed with an alternate illness, but it probably did not explain her CFS symptoms. Mood improved for those patients whose illness lessened. Conclusions: The prognosis for recovery was extremely poor for the severely ill subset of CFS patients. The majority showed no symptom improvement and only 4% of the patients recovered. Illness severity between Times 2 and 3 remained stable.

This sludy has two goals: one, to compare the resting end-tidal pCCb (PctCCh) and heart rate (HR) of chronic fatigue syndrome patients (CFS) with controls; two, to examine the effects of a mouthpiece and noseclips upon measurements of PelC02 and HR. Patients from the CFS Center came to the University Hospital pulmonary function laboratory for one testing session. Arterial (PaCCh), PetCOi, end-nasal (PenCOi) and HR were measured twice; both with and again without the subject breathing through the mouthpiece. We found that PcnCCb was greater and HR lower for both CFS and non-CFS groups when subjects were not confined by the mouthpiece. We conclude that there is no abnormality in the regulation of respiration in CFS patients. Changes in HR accompany changes in PetCOi in this study. Most likely, both result from anxiety associated with mouthpiece breathing.

Objective: Law enforcement represents a large population of workers who may be exposed to electronic control devices (ECDs). Little is known about the potential effect of exposure to these devices on respiration or cardiovascular response during current discharge. Methods: Participants (N=23) were trainees exposed to 5 seconds of an ECD (Taser X26®) as a component of training. Trainees were asked to volitionally inhale during exposure. Respiratory recordings involved a continuous waveform recorded throughout the session including during the exposure period. Heart rate was calculated from a continuous pulse oximetry recording. Results: The exposure period resulted in the cessation of normal breathing patterns in all participants and in particular a decrease in inspiratory activity. No significant changes in heart rate during ECD exposure were found. Conclusions: This is the first study to examine breathing patterns during ECD exposure with the resolution to detect changes over this discrete period of time. In contrast to reports suggesting respiration is unaffected by ECDs, present evidence suggests that voluntary inspiration is severely compromised. There is no evidence of cardiac disruption during ECD exposure.

Purpose : The aim of this study was to assess the utility of clinical assessment of respiratory muscle weakness in MS. Patients and methods : We studied 40 MS patients who performed pulmonary function tests using standard procedures and measures of respiratory muscle strength. Descriptive clinical indices included a history of detailed neurologic findings, including upper and lower extremity weakness, cerebellar signs, and evidence of cerebral lesions and other clinical signs including dependence in activities of daily living, shortness of breath, weak voice, dysarthria and dysphagia. We devised an index comprised of four clinical signs: the patient's report of difficulty in clearing pulmonary secretions and his report of a weakened cough, the examiner's observation of the patient's cough, and ability to count on a single exhalation. Results : Mean values of TLC (95 percent ±14) VC (91 percent ±19), and RV (106 percent ±34) were normal. By contrast, MVV (68 percent ±20), PImax (74 percent ±27) and PEmax (51 percent ±22) were decreased. Stepwise multiple regression indicated that the best single predictor of expiratory muscle weakness was the index score; the combination of index score, upper extremity weakness, and maximal voluntary ventilation accounted for 60 percent of the variance in PEmax. Conclusion : We conclude that clinical assessment is a better predictor of respiratory muscle weakness than spirometry and that a systematic clinical assessment supplemented by respiratory muscle assessment and MVV can uncover subtle respiratory muscle weakness in patients with MS.

This report presents a simple clinical method to quantify the pressure generated within ascites fluid and thus to examine the effect of that fluid upon lung volume. The intra-abdominal hydrostatic pressure (Pih) given in cm H2O is the height of the meniscus of a column of water above the anterior abdominal wall measured with the patient supine. Pih thus may be thought of as a pressure in excess of the height of the anterior abdominal wall. In 23 study subjects, Pih measured 7.0 +/- 4.8 cm H2O; Pih correlated inversely with all static volumes. Furthermore, abdominal compliance (measured as the ratio of 100 ml ascites fluid removed divided by the difference between Pih before and after fluid removal) correlated directly with functional residual capacity. We conclude that the effect of ascites upon respiratory function varies among patients; the variation may be explained in part by Pih.

Background: The severity of a patient’s asthma and the intensity with which he describes his dyspnea do not correlate. Objectives: There is an indirect relationship between airway function in asthma and the intensity of dyspnea; this relationship is found only when the measure of a patient’s general tendency to exaggerate the intensity of any somatic symptom is considered simultaneously. Methods: Lung function, including spirometry (forced expiratory volume in 1 s, FEV1) and plethysmography (airway resistance, Raw), dyspnea (Borg scale score) and the tendency to exaggerate (the somatosensory amplification scale score, SSAS) have been quantified in 42 stable asthmatic patients. Results: There was no correlation between the Borg score and any spirometric or plethysmographic measure in these subjects. By contrast, there was a moderate correlation between the Borg score and the SSAS (r = 0.36, p = 0.03). However, when FEV1 or Raw (abscissa) and Borg scores (ordinate) were converted to residuals, there was a moderate correlation between the residuals and the SSAS score (for FEV1, r = 0.33 and p = 0.05; for Raw, r = –0.36 and p = 0.03). Conclusion: A physician may make a reasonable estimate of an asthmatic patient’s lung function from the intensity of his complaint only if he – the physician – considers the patient’s tendency to symptom amplify as well.

It has been shown that patients with COPD require as long as 20 min for equilibration of oxygen tension to occur after changing the fraction of inspired oxygen (FIO2). To date, there have been no studies to determine the equilibration time for the PaO2 in mechanically ventilated patients with diffuse pneumonia. We studied seven patients (five males, two females) with radiographic evidence of diffuse pneumonia. All patients required mechanical ventilation. After introducing a change in FIO2, arterial blood gas values were measured at 5-min intervals for 30 min. Four patients achieved maximal change in PaO2 after 5 min, while four patients required 10 min. These results are similar to those found in patients with left ventricular failure who experience equilibration rapidly; however, patients with COPD experience it at a much slower pace. These observations have clinical importance when managing unstable patients where time is a critical element.

The reflex control of breathing can be modified behaviorally by the cortex, which receives information on respiratory movements and is able to alter ventilation by sending signals to the bulbopontine respiratory neurons and to spinal motor neurons. This behavioral control of respiration can interfere with reflex control during speaking and singing for example; but can also assist reflex control by enhancing responses to chemical stimuli and preventing apneas during wakefulness. It is also possible that behavioral control helps adjust ventilation and breathing patterns to minimize work expenditure and maximize gas exchange. Respiratory sensations are affected both by respiratory movements and by changes in chemoreceptor activity. Sensations increase with ventilation, particularly with greater respiratory efforts per breath and also grow as PCO2 rises. This behavioral control which might act to modify ventilation and breathing patterns to minimize respiratory sensations could help achieve an optimum compromise between ventilation and PCO2 levels.

Accessible online at: http://BioMedNet.com/karger The prevalence of obese adults is approximately 25% of the population in most countries of Western Europe [1]. More disquieting, as many as 55% of adults in the United States are overweight [2]. Obesity is the second leading cause of preventable deaths in that it predisposes people to hypertension, dyslipidemia, coronary artery disease, diabetes, and other diseases as well. Respiratory system manifestations of obesity, such as the obesity-hypoventilation syndrome (OHV) and obstructive sleep apnea, are less common but nevertheless of great clinical importance. The manner in which the respiratory and circulatory systems interact in obesity to cause alveolar hypoxia, pulmonary hypertension, and right ventricular failure is well documented in an older study [3]. Only a small percentage of people with severe obesity present with pulmonary disease, however. Attempts to identify those factors which predispose obese people to respiratory system dysfunction are of both academic interest and clinical use. The possibility that cardiopulmonary failure occurs only in those overweight subjects with predominately truncal obesity has often been raised. In this issue of Respiration De Lorenzo et al. [4] propose the technique of dual-energy-X-ray absorptiometry (DXA) as a tool to study body composition and fat distribution in man. They document in 16 obese subjects (none apparently with cardiopulmonary failure) both a positive correlation between lean body mass and lung volumes and a decrease in fat mass accompanying weight loss. Moreover, they note that the decrease in fat mass was sustained by a decrease in upper body fat. Their paper raises intriguing questions. Is there a statistical relationship between the loss of upper body fat and the increase in vital capacity after weight loss? How would these data compare with data obtained from obese subjects who clearly did manifest OHV? Would the FMTRN/ body height ratio be a better index with which to assess the effect of obesity upon respiratory mechanics than an FMTRN/FMTOT ratio? After all, the former ratio would serve as an index of the rotund body shape we empirically associate with OHV. How do DXA measurements compare as predictors of lung volume with simple measures of circumference and height which were also presented in the paper of de Lorenzo et al. [4]? Finally, would observations made with the DXA technique correspond to any genetic markers of obesity [5]. De Lorenzo et al. [4] have put forth a bold challenge to the pulmonary community to enhance our understanding of the relationship between obesity and cardiopulmonary dysfunction.

Objective To assess the reliability of maximal inspiratory pressure (P i max) and maximal expiratory pressure (P e max) in subjects with multiple sclerosis (MS) and healthy control subjects by identifying the number of testing sessions and the number of measurements needed in a single testing session to obtain consistent, reproducible results. Design A descriptive, comparative design with repeated measures was used. Setting Four sets of 10 P i max and 10 P e max measurements were obtained over a 4-week period from MS subjects in their homes. The same measurements were obtained from healthy control subjects in a private setting. Subjects Seventy-two MS patients and 61 healthy control subjects participated in the study. Measurement P i max and P e max values were obtained by using previously published methods. Results Mean P e max and P i max values for MS patients differed over the first three of the four testing sessions. By contrast, mean P e max and P i max values for healthy control subjects differed only when the first session values were compared with values from the last three sessions. For MS patients, P e max and P i max increased between the first and 10th trial during the first testing session, but not during the subsequent three sessions. Conclusions The results of this study suggest that several practice sessions should be provided in order to obtain reliable P e max and P i max values in persons with MS. At least one practice session should be provided for healthy control subjects before identifying a baseline.

The purpose of this study was to evaluate immune function through the assessment of lymphocyte subpopulations (total T cells, major histocompatibility complex [MHC] I- and II-restricted T cells, B cells, NK cells, MHC II-restricted T-cell-derived naive and memory cells, and several MHC I-restricted T-cell activation markers) and the measurement of cytokine gene expression (interleukin 2 [IL-2], IL-4, IL-6, IL-10, IL-12, gamma interferon [IFN-γ], and tumor necrosis factor alpha [TNF-α]) from peripheral blood lymphocytes. Subjects included two groups of patients meeting published case definitions for chronic fatigue syndrome (CFS)—a group of veterans who developed their illness following their return home from participating in the Gulf War and a group of nonveterans who developed the illness sporadically. Case control comparison groups were comprised of healthy Gulf War veterans and nonveterans, respectively. We found no significant difference for any of the immune variables in the nonveteran population. In contrast, veterans with CFS had significantly more total T cells and MHC II + T cells and a significantly higher percentage of these lymphocyte subpopulations, as well as a significantly lower percentage of NK cells, than the respective controls. In addition, veterans with CFS had significantly higher levels of IL-2, IL-10, IFN-γ, and TNF-α than the controls. These data do not support the hypothesis of immune dysfunction in the genesis of CFS for sporadic cases of CFS but do suggest that service in the Persian Gulf is associated with an altered immune status in veterans who returned with severe fatiguing illness.

Starling's law (the energy of muscle contraction is proportional to the initial fiber length) has been applied to contraction of inspiratory muscles. Its application to the expiratory muscles is difficult because both maximal length and maximal pressure development occur at total lung capacity (TLC). We hypothesize that decrease of both inspiratory (Pimax) and expiratory (Pemax) muscle strength in chronic ascites (CA) will reflect generalized muscle weakness and stretching of both the diaphragm and abdominal wall as well. To test this hypothesis, we evaluated Pimax and diaphragm length (at functional residual capacity) in 22 patients. Pemax, external oblique and transversus abdominus muscle lengths, and anterior abdominal wall muscle thickness were measured at TLC. We found Pimax (78 +/- 19% predicted), Pemax (61 +/- 17%), and--as an index of general muscle strength--handgrip strength (75 +/- 22%) all to be minimally reduced. Respiratory muscle strength did not correlate with any measurement of inspiratory/expiratory muscle length or thickness. With fluid removal, abdominal muscles shortened; diaphragmatic curvature decreased although diaphragm length was unchanged. Nevertheless, neither Pimax nor Pemax increased. Respiratory muscle strength depends upon generalized muscle strength more so than upon muscle length in CA patients.

Accessible online at: www.karger.com/journals/res Pela et al. [1] wrote an interesting article recommending daily oral N-acetylcysteine (NAC) as a preventive therapy for patients with chronic obstructive pulmonary disease (COPD). For three reasons, however, I do not share their enthusiasm for this therapy. First, support for the initial premise, namely that NAC may have a beneficial effect on COPD, is equivocal. Our recent review of this topic concluded that ‘evidence for efficacy is conflicting and, in general, provides minimal support for the clinical utility of N-acetylcysteine’ [2]. We interpreted at least two of the references which Pela et al. quoted as supportive of the hypothesis as being negative studies [3, 4]. The British Thoracic Society Research Committee study, for example, showed no statistical difference in the number of exacerbations between the placebo and treatment groups. Therefore, I would not have expected a positive outcome for this study. Second, in the Pela study the control group was not offered a placebo tablet. The study group received ‘standard therapy plus NAC, 600 mg once a day’ while the control group subjects received ‘standard therapy’ alone. How was the study presented and explained to each participant? How could study group subjects not have known that they were receiving an extra pill? Would not the study group subjects have had greater expectations than their control counterparts for their outcome because they were receiving an extra, experimental drug? This omission is critical because the outcome measures used in the Pela study, with the exception of spirometry, all require subjective verbal responses to questions regarding each subject’s perception of his own well-being. Third, the major end points of the study were subjective and based on the patients’ responses to the questionnaires used. The questionnaires were not well designed for the assessment of interindividual differences in the subjects’ perceptions of the severity of their symptoms; no details were given as to how the questionnaires were administered. Let us consider, for example, the grading of ‘mucus’ and ‘dyspnea’ in this study. Subjects were asked to grade both mucus and dyspnea as ‘unchanged’, ‘increased’ or ‘severely increased’ (the greater degree of worsening of mucus was described as ‘increased and purulent’). Subjects were given no opportunity to report any perceived decrease of either symptom. It is a well-known principle in the discipline of behavioral science that, to compare quantitative estimates of people’s perceptions of their feelings or symptoms, the perceptive range given by the questionnaire for each symptom must be set in the same way for all individuals. This principle, developed in the work of the exercise physiologist Gunnar Borg, has been elegantly reviewed [5]. The scale used in the Pela study, which offered the subject only three choices for the grading of his dyspnea or mucus production, does not provide an optimal perceptive range for the quantification of these symptoms. Data

Nagaan of de expiratiemusculatuur bij patienten met multipele sclerose, (ms) door middel van training kan worden versterkt, door vergelijking van de effecten van expiratietraining en schijntraining op de kracht van de expiratiemusculatuur.

Accessible online at: www.karger.com/journals/res Pressure support ventilation (PSV) reduces the work of breathing in patients with intrinsic lung disease. When such patients fail and require intubation, PSV facilitates the weaning process, thereby promoting extubation [1, 2]. By contrast, the role for PSV in the management of patients with respiratory failure but free from intrinsic lung disease is not defined. Many patients would conceivably fit into this category: postoperative patients with normal lung function and patients with neuromuscular diseases, for example. To this end, Vanpee et al. [3] have presented data in this issue of Respiration describing the effects of PSV when administered to healthy, awake volunteer subjects. Their subjects performed more respiratory work when actively assisting the inspiratory effort delivered by the ventilator (much in the same way a patient would augment the mechanical inhalation during either PSV or proportional assisted ventilation) when compared to work performed during a passive inhalation. By contrast, these subjects performed less work when they resisted the inspiratory effort of the ventilator. These data suggest that resisting mechanical inhalation would confer some benefit for the patient, namely reducing his inspiratory breathing work. It is difficult to draw a definitive conclusion from this paper regarding the effect of PSV upon breathing work during passive inhalation because control data, that is a measure of breathing work during spontaneous unassisted ventilation, is not given. The reader cannot determine whether or not the work of breathing during an actively assisted inspiration is actually more or less than the work done during spontaneous breathing. We are also not told to what degree dyspnea is associated with each experimental condition. The fact that relief of dyspnea is not necessarily associated with increasing levels of PSV in patients with lung disease would suggest that the relief of dyspnea is not a requisite for successful weaning during PSV [4]. The ranges of tidal volumes in this study were very great. Subjects breathed 15.8 liters/min during actively assisted breathing but only 6.9 liter/min during the resisted breathing trial. It is inconceivable that either dyspnea or arterial pCO2 would have been the same during all experimental conditions. While reduction of breathing work ought to be accompanied by a reduction of dyspnea, it is also true that pCO2 elevations are associated with worsening of dyspnea in normal subjects. Neither dyspnea scores nor measures of pCO2 are given for these subjects. From the above observations I would conclude that I cannot predict (1) which of these experimental trials would be associated with the greatest reduction of dyspnea and (2) which of these modes would be most favorable for either weaning or maintenance of the patient on long-term ventilation. Vanpee at al. [3] have presented greatly stimulating preliminary data. We encourage them and others to expand upon this work.

To evaluate the bioavailability of a new theophylline preparation suitable for once-a-day (od) oral administration, we performed a nonrandomized crossover study in which the absorption of the OD and a standard twice-a-day (bid) preparation were compared. Eight stable asthmatic patients, after having achieved steady-state, received an average of 975 mg of OD preparation at 8 pm. The protocol was later repeated with the same subjects receiving 487.5 mg of the bid preparation at 8 pm and again at 8 am using the same total dose. The maximal mean serum concentrations were 15.5±1.6 (SEM) µg/ml for the od preparation on the 8th hour and 12.7±2.2 for the bid regimen. The trough level was 7.4±1.2 µg/ml for the od regimen and 10.6±1.6 for the bid regimen. With either regimen, therapeutic theophylline levels could be observed throughout the 24-hour study period. Anhydrous theophylline may be administered as a single daily dose agent.

We compared tidal volume (VT) measured from the integrated airflow signal of a pneumotachygraph (PNTG) in ten patients, seated comfortably, with airway obstruction to VT, recorded simultaneously, by three chest-wall volume-displacement methods: two-channel magnetometer, isovolume calibration (mag-isov); respiratory inductance plethysmograph, isovolume calibration (rip-isov); and, inductance plethysmograph, least squares calibration (rip-l sq). There was no difference between VT, measured without PNTG, with each of the methods. When mouthpiece, noseclips, PNTG, and finally, dead space were included in a breathing circuit, VT increased to approximately one and one-half times that measured without the mouthpiece. Inspiratory volumes were measured with similar error by each method (mag-isov, 8.61 +/- 5.73 percent SD; rip-isov, 9.30 +/- 6.12 percent SD; rip-l sq, 8.43 +/- 6.27 percent SD). We conclude that in airway obstruction patients seated in a constant position, over the range of inspiratory volumes studied, error associated with chest wall volume-displacement methods is no greater than in normal subjects.

Volume-pressure diagrams during inflation with air and saline were made with the lungs of 6 control dogs and 24 dogs with acute alveolar injury induced by subcutaneous injection of 6 mg of N-nitroso-N-methylurethane pper kg of body weight 3 to 14 days before study. The extent of alveolar closure was estimated by measuring the mean linear intercept of the remaining open air spaces after inflation of the lung with liquid formalin at a pressure of 40 cm H2O. This alveolar closure was defined as irreversible. The volume-pressure diagrams and compliance data derived from them during the 3 to 4, 5 to 7, and 9 to 14 day periods after injection were analyzed and compared with the morphometric data. The diagrams with air inflation showed a progressive downward shift beginning with the 3 to 4 day period. This shift was at least partly independent of volume loss. The diagrams with saline inflation were unchanged during the 3 to 4 day period, but showed a downward shift, largely due to volume loss thereafter. Irrever...

An unusual patient with hypoxemia, hypercapnia, and right ventricular failure is presented. Minimal skeletal muscle weakness, although present, cannot explain hypercapnia. Muscle biopsy revealed diabetic microangiopathy. Carbon dioxide stimulation demonstrated a diminished hypercapnic ventilatory response. The patient benefited from progesterone therapy. In this unusual patient, mild muscular weakness, caused by diabetes, and central alveolar hypoventilation have acted in synergism to cause abnormal ventilation and right ventricular failure.

To examine the effect of abdominal distension upon the actions of both rib cage and abdomen, we made serial determinations of tidal volume with a chest wall volume-displacement method in 8 pregnant women. Enhancement of tidal volume, long recognized in pregnancy, was achieved usually by augmentation of rib cage volume displacement. By contrast, abdominal volume displacement during quiet breathing is not altered in a predictable fashion by the gravid state. Given these findings, we hypothesize that the increased diaphragmatic contraction of pregnancy is accompanied by the transmission of that force to the lower rib cage via the area of apposition and that diaphragmatic contraction accounts for enhancement of the tidal breath. Diminished abdominal compliance might contribute to the augmentation of rib cage volume displacement as well. Konno-Mead diagrams suggest that this hypothesis is true in some, but not all, subjects.

SUMMARY Ventilation (liters of air per minute) increases during an acute attack of asthma. Hypocapnia is the rule, although eucapnia may occur. This suggests both that respiratory center output is increased and that acidemia is not the major stimulus to augmented respiration. Mechanical receptors responding to change in end-expiratory respiratory system volume or airway dimensions, cortical stimulation to the medullary respiratory centers, and possibly hypoxemia function in concert to regulate ventilation in asthma. Newer laboratory techniques permit independent assessment of chemical and cortical components of ventilatory drive. These techniques have provided fresh insights into the effects of various therapeutic interventions upon respiration in asthma.

40 normal subjects performed spirometry, maximum voluntary ventilation (MVV), and tests of static inspiratory (Pi max) and expiratory (Pe max) respiratory muscle pressure. Forced expiratory volumes in 0.5 (FEV0.5), in 0.75 (FEV0.75), and 1 sec (FEV1) correlated significantly with MVV (r = 0.805, 0.804, 0.779, respectively). When Pi max was considered as a second independent variable, the probability of predicting MVV from timed forced expiratory volumes was enhanced (r = 0.914, 0.900 and 0.872 for FEV0.5, FEV0.75, and FEV1, respectively). Statistical analysis indicated that multiple regression with Pi max was superior to regression with timed forced expiratory volume alone in the prediction of MVV. For any given FEV1, however, Pi max was widely dispersed (range: -60 to -200 cm H2O). MVV values, expressed as percentage difference between largest and smallest value, varied less than did Pi max. Pe max, vital capacity, height and age did not enhance the ability of timed forced expiratory volumes to predict MVV. These data indicate that while respiratory muscle strength is important for sustaining maximal ventilation, the MVV is not a sensitive indicator of respiratory muscle strength.

To investigate the mechanism for hyperventilation in two common but dissimilar conditions, asthma (A) and lobar pneumonia (P), we examined the ventilatory pattern in 17 A and six P subjects. When acutely ill, hyperventilation (PaCO2) was similar in the two groups. Minute ventilation (VE) however, was slightly greater in group A than in P. In A patients, measurements of occlusion pressure (dP/dT) and inspiratory flow rate (VT/ti) during quiet breathing showed enhancement of respiratory center output. By contrast, in P patients, dP/dT and VT/ti were not elevated. Tidal volume (VT) was 0.59 +/- 0.19 L in A; 0.45 +/- 0.09 in P. Respiratory rate was increased in both groups. With supplementary oxygen therapy, neither VE nor PaCO2 changed in either group. The mechanism for the increased ventilatory drive in group A is unclear. Most likely, reflexes initiated by either bronchospasm or by the sudden increase of end-expiratory lung volume (EELV), not operative in P, account for the increased respiratory center output seen in A. To examine the latter possibility, we studied the ventilatory pattern at both normal and increased EELV in six nonasthmatic subjects. Both dP/dT and VT/ti were increased in all subjects after elevation of EELV. Thus, changes in EELV may be important for the regulation of ventilation during bronchospasm.

Increased (more positive) end-expiratory and decreased (more negative) end-inspiratory values for intrapleural pressure (Ppl) invariably accompany acute bronchoconstriction. We hypothesize that both the increase in vital capacity (VC) and the decrease in residual volume (RV) observed after dilation of the central airways in patients with reversible obstruction of the airways result, in part, from a restoration of normal Ppl during unforced exhalation. To test this hypothesis, we examined the end-expiratory Ppl during breathing at rest in ten emphysematous and eight asthmatic subjects before and after inhalation of isoproterenol. The VC increased by 0.38 L after therapy, and the specific airway resistance and the RV decreased by 6.8 cm H 2 sec and 0.63 L, respectively. Total lung capacity was unchanged. The response of the VC to administration of isoproterenol is an important sequel to dilation of the large airways. Bronchioles close at a critical Ppl during exhalation. Because Ppl normalizes with administration of isoproterenol, this closure may be delayed to a lower pulmonary volume even if improvement in the function of peripheral airways does not occur.

Augmentation of inspiratory muscle strength (Pimax) represents an adaptive response to airway obstruction. We explore the possibility that respiratory muscle weakness may herald hospital admission during acute bronchospasm. The Pimax measured 81 +/- 25 percent of a predicted value in 20 patients with acute bronchospasm (forced expiratory volume in one second, 36 +/- 17 percent predicted). Pimax was related to both hyperinflation (functional residual capacity, as percent predicted) and body weight (subjects were 122 +/- 29 percent ideal body weight), but not to the degree of airway obstruction per se. Furthermore, measurements of axial (craniocaudal) motion of the rib cage and asynchrony of rib cage and abdominal motions during tidal breathing did not correlate with either the degree of air flow obstruction or Pimax. We conclude that little if any respiratory muscle weakness occurs with bronchospasm. Furthermore, Pimax does not correlate with the degree of airway obstruction and does not explain abnormalities of rib cage and abdominal motion associated with asthma.

Oxygen consumption and carbon dioxide production were measured in 29 asthmatic subjects. Minute ventilation was measured by a rib cage and abdomen-diaphragm displacement method. Expired gases were collected via a tight-fitting mask. Minute ventilation, oxygen consumption, and carbon dioxide production all increased when subjects inspired room air via a mouthpiece (when compared with a tight-fitting mask). By contrast, minute ventilation and carbon dioxide production both decreased when supplementary oxygen replaced room air via the tight-fitting mask (p less than 0.001). No consistent changes in either inspiratory work (estimated from measurement of pleural pressure during quiet breathing), airway resistance, or physiologic dead space could be seen to accompany changes in minute ventilation. It is concluded that the oxygen cost of breathing in asthma is substantial.

The clinical significance of respiratory-system load-compensation is unknown. We have measured the responses to random presentation of single, elastic inspiratory loads in 36 subjects: 8 normal personnel (N), 9 with obesity (O), 10 with chronic renal failure under hemodialysis (H), 5 with pneumonia (P), and 4 with interstitial lung disease (CILD). We have expressed these responses as: (1) the ratio of elastance (or rigidity) of the system during loaded breathing to the elastance without loading (E'RS/ERS); (2) the ratio of tidal volume (VT) achieved when breathing from an inspiratory load to the VT predicted in the absence of load compensation (VTL/VTP); (3) the ratio of inspiratory flow rates during loaded and unloaded breaths; (4) the ratio of inspiratory time of loaded and unloaded breaths. We found E'RS/ERS in the O, H and P groups less than that of either CILD patients or N controls (F = 6.79; p less than 0.001). Passive elastance (ERS) although greater in groups O and H than in N (F = 3.88; p less than 0.025) did not account for the difference i E'RS in all groups. When expressed as VTL/VTP, the response to a 37-cm H2O/l load for groups H, O and P was less than that for N (F = 5.51; p less than 0.05). Diminished inspiratory time was observed in H, O and P patients when inspiring from this load. In contrast, inspiratory flow did not differ from that of normal subjects. Nerve conduction velocity was slightly reduced or normal in the H patients. Respiratory load compensation is deficient in H, O and P patients. The mechanism, which does not involve peripheral neuropathy, is unclear.