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There is considerable intersubject variability in the perceived intensity of breathlessness for a given level of activity among patients with chronic airflow limitation (CAL). To examine possible factors contributing to this variability we compared breathing pattern parameters, dynamic operational lung volumes, and Borg dyspnea ratings in 23 patients with severe CAL and in 10 healthy age-matched normal subjects during cycle ergometry to symptom-limitation. Patients with CAL had significantly (p < 0.01) higher levels of ventilation (% maximal voluntary ventilation) for a given work rate (slope of VE(%MVV)/WR(% pred max) = 1.51 +/- 0.18 versus 0.63 +/- 0.10; mean +/- SEM) and greater dynamic lung hyperinflation (DH) (change [delta] in end-expiratory lung volume [EELVdyn] = +0.31 +/- 0.11 L versus -0.16 +/- 0.22 L). Compared with normal subjects at a standardized VE (30 L/min), the CAL group was more breathless Borg = 4 +/- 1 versus 2 +/- 1, p < 0.01) and hyperinflated (EELVdyn = 75 +/- 3 versus 46 +/- 6% TLC, p < 0.001; end-inspiratory lung volume [EILVdyn] = 85 +/- 3 versus 67 +/- 5% TLC, p < 0.01). Within the CAL group, change in Borg ratings correlated with delta VE(%MVV) (r = 0.77, p < 0.001) and with slope of VE(%MVV)/WR(% pred max) (r = 0.48, p < 0.01). Regression analysis selected delta EILVdyn (or delta inspiratory reserve volume [delta IRVdyn]) from various dynamic ventilatory parameters as the strongest predictor of delta Borg (r = 0.63, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exertional breathlessness in patients with chronic airflow limitation. The role of lung hyperinflation. 823 75

The purpose of this study was to examine potential contributing factors to breathlessness during bronchoconstriction, in particular, to evaluate the role of lung hyperinflation. We also wished to elucidate qualitative aspects of the unpleasant sensory experience and to identify factors that contribute to intersubject variability in subjective and objective assessments of airflow obstruction. We studied sensory-mechanical interrelationships during and after induced bronchoconstriction in 21 subjects with mild stable asthma. Breathlessness (Borg scale), spirometry, and inspiratory capacity (IC) were measured after each dose during methacholine bronchoprovocation to a maximal change (delta) in FEV1 of 50%. Breathing pattern, specific airway resistance (SRaw), plethysmographic thoracic gas volume, and maximal inspiratory mouth pressure (MIP) were recorded at baseline, at maximal response, and at full symptom recovery. End-expiratory lung volume (EELV) was derived from IC. Borg increased from 0.4 +/- 0.1 (very, very slight) at baseline to 5.0 +/- 0.5 (severe) at maximal bronchoconstriction (mean +/- SEM, p < 0.001). FEV1 fell significantly (p < 0.001) to 48% predicted at maximal response. Of the 21 subjects, 19 reported increased inspiratory rather than expiratory difficulty and predominantly described sensations of reduced inspiratory capacity and unrewarded inspiratory effort. Stepwise multiple regression analysis using delta Borg (outcome variable) versus changes in spirometry, SRaw, IC, and breathing pattern components, selected delta IC as the principal contributing factor: delta Borg = 0.09 (delta IC, %fall); n = 193, r = 0.86, p < 0.001. delta IC continued to contribute significantly (p < 0.001) to the variance in Borg ratings after accounting for delta FEV1, and it was the strongest predictor of symptom recovery (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Breathlessness during acute bronchoconstriction in asthma. Pathophysiologic mechanisms. 825 84

Exercise in chronic airflow limitation (CAL) is often limited by symptoms before the physiologic boundaries of maximal ventilatory or cardiovascular capacities are attained. Symptom amelioration should translate directly into improved exercise performance. We studied the impact of a 6-wk supervised multimodality endurance exercise program (EXT) on perceived breathlessness (B) and leg effort (LE) and sought a physiologic rationale for symptom improvement. Thirty patients with CAL (FEV1/FVC = 42 +/- 2%, mean +/- SEM) were tested before and after EXT. Their responses were compared with those of a matched control group (n = 30; FEV1/FVC = 44 +/- 2%) after a nonintervention period. Testing included pulmonary function tests, chronic dyspnea evaluation (Baseline/Transition Dyspnea Index [BDI/TDI]), and graded cycle exercise with cardioventilatory monitoring and Borg scaling of B and LE. Spirometry did not change (delta) post-EXT. EXT significantly (p < 0.001) reduced chronic breathlessness (TDI = +2.8 +/- 0.3) compared with control (TDI = 0.0 +/- 0.3). Exertional symptoms of B and LE also fell (p < 0.01) after EXT (slopes of B and LE relative to VO2 fell by 14 and 23%, respectively; delta B/VO2 was associated with delta LE/VO2, r = 0.52, p < 0.01). Post-EXT slopes of B over ventilation (VE) also decreased by 10% (p < 0.025). Total cycle work increased 142 +/- 70% (p < 0.001) post-EXT and correlated primarily with delta B/VO2 (r = -0.64, p < 0.001). The best correlate of delta B/VO2 was delta VE/VO2 (r = 0.47, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The impact of exercise reconditioning on breathlessness in severe chronic airflow limitation. 852 Jul 69

Patients with congestive heart failure (CHF) suffer from respiratory muscle weakness which may contribute to dyspnea. Nasal continuous positive airway pressure (NCPAP) can improve left ventricular ejection fraction (LVEF) and reduce dyspnea in patients with CHF and Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) but its effects on respiratory muscle strength are not known. We therefore studied the effects of NCPAP on maximal inspiratory and expiratory pressures (MIP and MEP, respectively), LVEF, dyspnea, and fatigue in patients with chronic CHF and CSR-CSA over 3 mo. Eight patients were randomized to control and nine to nightly NCPAP. There were no significant changes in any of these factors in the control group during the study. In contrast, among the NCPAP group, MIP increased from 79.3 +/- 8.1 to 90.7 +/- 10.4 cm H2O (mean +/- SEM; p < 0.02), LVEF increased from 24.0 +/- 4.0 to 32.6 +/- 6.6% (p < 0.02) and symptoms of dyspnea and fatigue were alleviated. However, MEP did not change. In addition, the number of apneas and hypopneas decreased from 49 +/- 11 to 17 +/- 7 per hour of sleep (p < 0.001) and mean low Sao2 during sleep increased from 87.9 +/- 1.0 to 93.0 +/- 1.0% (p < 0.01). Our data indicate that nightly application of NCPAP in patients with CHF and CSR-CSA improves inspiratory muscle strength and LVEF, and relieves dyspnea and fatigue.
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PMID:CPAP improves inspiratory muscle strength in patients with heart failure and central sleep apnea. 854 29

The Lelystad virus or one of two US isolates (VR2385, VR2431) of porcine reproductive and respiratory syndrome virus were given intranasally to 25 4-week-old cesarian-derived colostrum-deprived pigs. Pigs from these groups were necropsied at 1, 2, 3, 5, 7, 10, 15, 21, or 28 days postinoculation. The Lelystad virus and VR2431 induced mild transient pyrexia, dyspnea, and tachypnea. VR2385 induced labored and rapid abdominal respiration, pyrexia, lethargy, anorexia, and patchy dermal cyanosis. All three isolates induced multifocal tan-mottled consolidation involving 6.8% (n = 9; SEM = 3.4) of the lung for Lelystad, 9.7% (n = 9, SEM = 2.7) of the lung for VR2431, and 54.2% (n = 9, SEM = 4.4) of the lung for VR2385 at 10 days postinoculation. Characteristic microscopic lung lesions consisted of type 2 pneumocyte hypertrophy and hyperplasia, necrotic debris and increased mixed inflammatory cells in alveolar spaces, and alveolar septal infiltration with mononuclear cells. Lymphadenopathy with follicular hypertrophy, hyperplasia, and necrosis was consistently seen. Similar follicular lesions were also seen in Peyer's patches and tonsils. Lymphohistiocytic myocarditis and encephalitis were reproduced with all three isolates. Clinical respiratory disease and gross and microscopic lung lesion scores were considerably and significantly more severe in the VR2385-inoculated pigs. All three viruses were readily isolated from sera, lungs, and tonsils throughout the 28 days of the study. The lymphoid and respiratory systems have the most remarkable lesions and appear to be the major site of replication of these viruses. This work demonstrated a marked difference in pathogenicity of porcine reproductive and respiratory syndrome isolates.
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PMID:Comparison of the pathogenicity of two US porcine reproductive and respiratory syndrome virus isolates with that of the Lelystad virus. 859

Seven repair technicians (RT, site A) repeatedly exposed to facsimile machine fume developed recurring sore throat, fever, lymphadenopathy, chest tightness, dry cough, and dyspnea. The fume concentration was low (0.6 mg/m3 of breathing-zone air) but it contained butyl methacrylate (BMA), a known skin sensitizer. Although chest radiographs were normal, three of the seven RT-A had lung crackles and spirometric abnormalities, and increased serum levels of immunoglobulins IgE or IgM. Symptoms and most other abnormalities improved when exposure to BMA was stopped. We later evaluated workers in two other sites (B and C). Six RT-B had daily contact with BMA fume (0.14 to 0.40 mg/m3 of air) at a field repair depot. Six administrative and six sales staff members (AS-B, SS-B) without regular fume exposure served as controls. All RT-B had elevated serum IgE levels (202+/-69 U/mL [SEM]; normal <41 U/mL). IgE and fume levels were positively correlated (r=0.83). four RT-B had lung crackles, but few symptoms and normal results of spirometry. The crackles cleared 8 weeks after substitution of a BMA-free paper, but IgE levels remained high (201+/-69). The nonexposed AS-B and SS-B had no crackles. Their IgE levels were normal (19+/-4 U/mL [SEM]; p<0.01). The crackles suggest BMA fume might have caused inflammation in terminal airways units. The significance of the IgE elevations is also uncertain since this class of antibodies is usually associated with asthma, not pneumonitis. In view of these uncertainties, BMA was eliminated from the facsimile transceiver process. Follow-up of group C workers (n=32) found no symptoms, lung crackles, or abnormal results of spirometry. However, IgE concentrations were elevated in 15 and remained so for 21 months, perhaps because of continuing exposure to residual low levels of BMA. These findings suggest that BMA-bearing facsimile fume caused increased IgE levels in RT at sites A, B, and C, and might have resulted in permanent lung injury if such exposure had continued.
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PMID:Pulmonary abnormalities and serum immunoglobulins in facsimile machine repair technicians exposed to butyl methacrylate fume. 863 24

Respiratory rehabilitation improves exercise capacity and quality of life in younger patients but is untried in the aged. We aimed to: (a) assess repeatability of the 6-minute walk test, factors affecting it and its relation to quality of life in elderly patients with chronic obstructive airways disease (COAD); (b) assess compliance of such patients with an intensive respiratory rehabilitation protocol; (c) pilot the assessment of the effect of respiratory rehabilitation on the 6-minute walk test in these patients. Seventeen subjects with stable, symptomatic COAD were recruited, 15 (six men), 70-89 (mean 76) years, completed the study. Mean (standard deviation) 1-second forced expiratory volume (FEV1) = 49 (5)% predicted. Six-minute walk tests were repeated single-blind, 2-10 days apart. Quality of life was measured using Guyatt respiratory questionnaire. Patients underwent 12 weeks incremental respiratory rehabilitation (x4/day step-ups, unweighed arm raises, inflating balloons). Baseline 6-minute walk was repeatable and was correlated with the log Guyatt dyspnoea score (r = 0.65, p = 0.006). In multiple regression neither age nor FEV1 predicted walk distance: body mass index, maximal expiratory mouth pressure; calorie intake. Mean (SEM) 6-minute walk distance after-rehabilitation was greater than baseline (p = 0.003). Elderly patients with COAD tolerate intensive respiratory rehabilitation and a controlled, blinded study is needed.
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PMID:Respiratory rehabilitation, exercise capacity and quality of life in chronic airways disease in old age. 867 May 23

Lung volume reduction surgery (LVRS) in patients with severe lung emphysema restores the thoracic configuration to a more normal functional capacity. The aim of this study was to investigate whether reduction in intrathoracic volume by LVRS improves the inspiratory muscle force generation of the respiratory pump. Pulmonary function tests, maximal inspiratory mouth pressure (MIP), sniff nasal inspiratory pressure (SNIP), sniff transdiaphragmatic pressure (Pdi), and inspiratory mouth occlusion pressure (P0.1) were measured in 17 emphysematous patients (mean (+/- SEM) age 53 +/- 2 yrs) before and 1 month after LVRS. The mean value of forced expiratory volume in one second (FEV1) increased (0.82 +/- 0.07 vs 1.12 +/- 0.08 L; p < 0.0001), whilst there was a decrease (p < 0.0001) in residual volume (RV) (337 +/- 31 vs 250 +/- 21 % of predicted), functional residual capacity (FRC) (210 +/- 9 vs 159 +/- 9% pred), and total lung capacity (TLC) (138 +/- 6 vs 110 +/- 5% pred). The mean value of MIP increased by 52% from 4.8 +/- 0.4 to 7.3 +/- 0.6 kPa (p < 0.001), the mean value of SNIP increased by 66% from 3.9 +/- 0.4 to 6.5 +/- 0.5 kPa (p < 0.001), and the mean value of Pdi increased by 28% from 6.0 +/- 0.6 to 7.7 +/- 0.8 kPa (p < 0.05) after LVRS. P0.1 decreased on average by 24% from 0.46 +/- 0.03 to 0.35 +/- 0.02 kPa after LVRS. No significant correlations were found between inspiratory muscle (MIP, SNIP, Pdi) and respiratory drive (P0.1) indices, lung function data, 6 min walk distance, or dyspnoea score. In conclusion, the observed clinical improvement of patients with severe emphysema after lung volume reduction surgery results, in part, from an increased ability of the inspiratory muscles to generate force, which is paralleled by a significant decrease in central respiratory drive.
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PMID:Effect of surgical lung volume reduction on respiratory muscle function in pulmonary emphysema. 888 88

Previous exercise training studies in patients with chronic congestive heart failure (CHF) were performed for periods lasting > 2 months, and effects of activity restriction on exercise induced-benefits were not systematically assessed. With one exception study, patients were not reported to be transplant candidates. In this random-order crossover study, effects of 3 weeks of exercise training and 3 weeks of activity restriction on functional capacity in 18 hospitalized patients with severe CHF [(mean +/- SEM) age 52 +/- 2 years; ejection fraction 21 +/- 1%; half of them on a transplant waiting list] were assessed. The training program consisted of interval exercise with bicycle ergometer (15 minutes) 5 times weekly, interval treadmill walking (10 minutes), and exercises (20 minutes), each 3 times weekly. With training, the onset of ventilatory threshold was delayed (p < 0.001), with increased work rate by 57% (p < 0.001) and oxygen uptake by 23.7% (p < 0.001). On average, there was a 14.6% decrease in slope of ventilation/carbon dioxide production before the onset of ventilatory threshold (p < 0.05), and ventilatory equivalent of carbon dioxide production by 10.3% (p < 0.01). At the highest comparable work rate (56 +/- 5 W) the following variables were decreased: heart rate (7.3%; p < 0.05), lactate (26.6%; p < 0.001), and ratings of perceived leg fatigue and dyspnea (14.5% and 16.5%; p < 0.001 each). At peak exercise, oxygen uptake was increased by 19.7% (p < 0.01) and oxygen pulse by 14.2% (p < 0.01). There was a correlation of baseline peak oxygen uptake and increase of peak oxygen uptake due to training (r = -0.75; p < 0.004). Independently of the random order, data after activity restriction did not differ significantly from data measured at baseline. Patients with stable, severe CHF can achieve significant improvements in aerobic and ventilatory capacity and symptomology by short-term exercise training using interval exercise methods. Impairments due to activity restriction suggest the need for long-term exercise training.
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PMID:Effects of short-term exercise training and activity restriction on functional capacity in patients with severe chronic congestive heart failure. 891 81

We compared qualitative aspects of the sensory experience of exertional breathlessness in normal subjects and in patients with chronic airflow limitation (CAL) and sought a physiologic rationale for these. Twelve patients (66 +/- 2 yr of age, mean +/- SEM) with severe CAL (FEV1 = 37 +/- 5% predicted) and 12 age-matched normal subjects (FEV1 = 103 +/- 5% predicted) were studied. Perceived inspiratory difficulty (BorgIN), inspiratory effort (esophageal pressure expressed as a fraction of maximal esophageal pressure at isovolume [Pes/PImax]), breathing pattern, and operational lung volumes (end-expiratory/inspiratory lung volumes [EELV/EILV]) were measured during symptom-limited incremental cycle exercise testing and compared at a standard VO2 of 50% predicted maximum in normal subjects and in patients with CAL. Qualitative descriptors of breathlessness were selected immediately after exercise. Breathlessness was qualitatively different between normal subjects and patients with CAL. Both normal subjects and patients with CAL chose descriptors of increased "work/effort" and "heaviness" of breathing; however, only patients with CAL consistently chose descriptors denoting "increased inspiratory difficulty" (75%), "unsatisfied inspiratory effort" (75%), and "shallow breathing" (50%). Stepwise regression analysis identified the ratio of Pes/PImax to VT/predicted VC as the strongest correlate of standardized BorgIN (n = 24, r = 0.86, p < 0.001). This latter measurement, which reflects the relationship between effort and ventilatory output, correlated strongly with dynamic EELV/TLC at isotime (r = 0.78, p < 0.001). In conclusion, the qualitatively discrete respiratory sensations of exertional inspiratory difficulty peculiar to patients with CAL may have their origins in thoracic hyperinflation and the resultant disparity between inspiratory effort and ventilatory output.
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PMID:Qualitative aspects of exertional breathlessness in chronic airflow limitation: pathophysiologic mechanisms. 900 Dec 98


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