Health Study, 65 yr of age and older, sampled from four communities. ... were age, current smoking, self-reported fair to poor general health, and waist size.
Respiratory Muscle Strength in the Elderly Correlates and Reference Values PAUL L. ENRIGHT, RICHARD A. KRONMAL, TERI A. MANOLlO, MARC B. SCHENKER, and ROBERT E. HYATI for the Cardiovascular Health Study Research Group Cardiovascular Health Study Coordinating Center, Seattle, Washington
Maximal inspiratory pressure (MIP) was assessed in 4,443 ambulatory participants of the Cardiovascular Health Study, 65 yr of age and older, sampled from four communities. Maximal expiratory pressure (MEP) was also measured in 790 participants from a single clinic. Positive predictors of MIP included male sex, FVC,handgrip strength, and higher levels of lean body mass (or low bioelectric resistance). Negative predictors were age, current smoking, self-reported fair to poor general health, and waist size. Both participant and technician learning effects were noted, but there was no independent effect of race, hypertension, cardiovascular disease, or diabetes. A healthy subgroup was identified by excluding current smokers, those with fair to poor general health, or an FE\!, less than 65% of predicted. Mean values determined from the healthy group were 57/116 cm H20 (MIP/MEP) for women, and 83/174 for men. Lower limits of the normal range (fifth percentiles) were 45 to 60% of the mean predicted values. The reference equations derived from this group of healthy 65 to 85-yr-olds may be used by pulmonary function laboratories and respiratory therapists who evaluate the respiratory muscle strength of elderly patients. Enright PL, Kronmal RA, Manolio TA, Schenker MB, Hyatt RE for the Cardiovascular Health Study Research Group. Respiratoty muscle strength in the elderly: correlates and reference values. Am J Respir Crit Care Med 1994; 149:430-8.
The measurement of maximal respiratory pressures (MRP) is now a routine procedure in many pulmonary function laboratories. Maximal inspiratory pressure (MIP) is an index of the strength of the diaphragm, whereas maximal expiratory pressure (MEP) mea(Received in original form February 19, 1993 and in revised form July 13, 1993) Participating Institutions and Principal Staff: Forsyth County, NC-Bowman Gray School of Medicine of Wake Forest University: Gregory L. Burke, Marie E.Cody, R. Gale Cruise, Walter H. Ettinger, Curt D. Furberg, Gerardo Heiss, H. Sidney Klopfenstein, David S. Lefkowitz, Mary F. Lyles,Maurice B. Mittelmark, Grethe S.Tell, James F.Toole; Sacramento County, CA-University of California, Davis: William Bommer, Marshall Lee, John Robbins, Marc Schenker; Washington County, MD-The JohnsHopkins University: R.Nick Bryan,Trudy L. Bush, Joyce Chabot, George W. Comstock, Linda P. Fried, PearlS.German, Joel Hill, Steven J.Kittner, Shiriki Kumanyika, Neil R.Powe, Thomas R.Price,Robert Rock, Moyses Szklo; Allegheny County, PA-University of Pittsburgh: Janet Bonk, Julie Thompson-Dobkin, Diane G. lves, Charles A. [unqreis, Lewis H. Kuller, Robert H. McDonald, [r., Elaine Meilahn, Peg Meyer, Anne Newman, Gale H. Rutan, Richard Schulz,Vivienne E.Smith, Sidney K.Wolfson; Echocardiography Reading Center-University of California, Irvine: Hoda Anton-Culver, Julius M. Gardin, Margaret Knoll, Tom Kurosaki, Nathan Wong; Ultrasound Reading CenterNew England Deaconess Hospital: Daniel H. O'Leary, Joseph F. Polak, Jeffrey Potter; Blood Analysis Laboratory-University of Vermont: Edwin Bovill, Elaine Cornell, Paula Howard, Russell P.Tracy; Pulmonary Function Reading CenterUniversity of Arizona, Tucson: Paul Enright, Sheila Toogood; ECG Reading Center-University of Alberta, Edmonton: Kris Calhoun, Harry Calhoun, Patty Montague, Farida Rautaharju, Pentti Rautaharju; Coordinating CenterUniversity of Washington, Seattle: Nemat O. Borhani, Annette L. Fitzpatrick, Bonnie K. Hermanson, Richard A. Kronmal, Bruce M. Psaty,David S. Siscovick, Lynn Shemanski, Patricia W. Wahl; NHLBI Project Office: Diane E. Bild, Teri A. Manolio, Peter J. Savage, Patricia Smith.
Supported by Contracts NOl-87079 through NOl-87086 from the National Heart, Lung, and Blood Institute. This report is dedicated to the memory of Philip Weiler. Dr. Weiler was a compassionate clinician, enthusiastic researcher, and Principal Investigator at the Sacramento CHS Field Center. Correspondence and requestsfor reprints should be addressedto Richard Kronmal, Ph.D., CHS Coordinating Center, Room 530, 1107 NE 45th St., Seattle, WA 98105. Am
J Respir Crit Care Med Vol 149. pp 430-438, 1994
sures the strength of abdominal and intercostal muscles. The primary indications for MRP tests are to quantitate the degree of respiratory muscle weakness present in patients who have dyspnea and respiratory failure, who are malnourished, or who are known to have neuromuscular diseases such as myasthenia gravis, Guillian Barre syndrome, amyotrophic lateral sclerosis, stroke, polio, or quadriplegia (1).Other uses include evaluation of unexplained reductions in the VC or maximal voluntary ventilation (MVV), and to predict the success of weaning a patient from mechanical ventilation (MIP) in the intensive care unit, or the ability of a patient to cough and bring up secretions (MEP). During the last 10yr, several other investigators have measured MRPs in younger age groups (2-4), and in patients with various lung and neuromuscular diseases. Reference values for MRPs for persons older than 65 yr of age are currently based on studies of only a few dozen volunteer subjects (5-8). The between-subject variability was high in these studies, and there was no consensus regarding the effects of age, height, weight, obesity, or cigarette smoking on MRPs. The Cardiovascular Health Study (CHS), a multicenter, prospective study of cardiovascular risk factors and disease in persons 65 yr of age and older, provided an opportunity to measure maximal respiratory pressures in a large population-based sample of ambulatory elderly persons (9). The objectives of this report are (1) to describe the distribution of MIP and MEP in this population sample and in a healthy subgroup, (2) to identify correlates of MIP and MEP in the elderly, and (3) to derive reference values and lower limits of the normal range for MIP and MEP from the healthy subgroup.
METHODS Recruitment . Participants in the Cardiovascular Health Study were selected using a Medicare eligibility list provided by the U.S. Health Care Financing Ad-
Enright, Kronmal, Manolio, et 01.: Respiratory Muscle Strength in the Elderly ministration (HCFA)for the four participating communities: Forsyth County, North Carolina; Pittsburgh, Pennsylvania; Sacramento County, California; and Washington County, Maryland. Potential participants were selected randomly from the four areas; 5,201 men and women were recruited and examined. All persons 65 yr of age and older in the household of a sample person were invited to participate. The following were exclusion factors: institutionalization, terminal illness, likely to move from the area during the next 3 yr, or inability to walk, communicate, or give informed consent. Potential participants were sent an explanatory letter, interviewed by telephone to determine eligibility, and then scheduled for the baseline clinic examination at the field center. Among those contacted and eligible, 57.6% were enrolled. Enrolled CHS participants were younger, more educated, and more likely to be married than those who refused or were ineligible (9). The research protocol was reviewed and approved by the institutional review board for human studies of each clinical center, and a complete informed consent was obtained from all participants. Participation The number of CHS participants enrolled from May 1989 to June 1990 was 5,201; 45% were men and 4% were black (145 women and 94 men). We did not obtain MIP measurements from 564 participants (11%), and other data were missing for 194 participants, leaving 4,443 participants (85.4%) for analysis of MIP results. MEP tests were obtained from 790 of 1,318 participants seen at the Sacramento clinic. MEP tests were not done by the others because of time/scheduling constraints. No adverse effects from performing this test (such as syncope) were reported. Technician Training and Monitoring Technicians were trained and certified centrally prior to the start of the study using the CHS Manual of Operations for Pulmonary Function Testing as a textbook. Training met the requirements of NIOSH for spirometry testing, including 16 h of workshops and lectures, and a written and practical examination. Fifteen technicians performed the majority of the MIP tests at the four clinics, and five technicians at the Sacramento clinic performed the MEP tests. Equipment Design The MRP-PC system (Scientific and Medical Instrument Co., Doylestown, PAl was used to measure MRPs. It consists of a cylindrical hard plastic mouthpiece adaptor connected to a Marshalltown 83KC-37pressure gauge and a solid-state pressure transducer. A hole (leak) 1 mm in diameter and one-fourth inch long is drilled in the mouthpiece adaptor, which results in a flow of 220 mils at 100 cm H20 , designed to prevent the participant from sustaining pressure with their cheeks (5). Calibration of the MRP transducer was checked each week against the mechanical gauge reading at plus and minus 150 cm H20 . The methods and results of spirometry testing are reported separately (10). Baseline Interview and Clinical Examination Participants were asked to fast for 12 h prior to the morning interview and examination. After a fasting blood sample was drawn and glucose load given, pulmonary function testing and other examination components were scheduled throughout the morning. Examination components included seated and postural blood pressure, resting 12-lead ECG, echocardiography for measurement of left ventricular mass (11), carotid ultrasound, and a physical examination. Anthropometric measurements included: standing height without shoes, sitting height, weight, and hip and waist circumference. Trainedinterviewers completed a subset of the standardized ATS DLD-78 Respiratory Questionnaire (12). Self-reported general health was assessed by asking the question, "Would you say, in general, your health is: excellent, very good, good, fair, or poor:' Handgrip strength was measured in triplicate, first in the dominant and then in the nondominant hand, using a Jamar dynamometer (Asimow Engineering, Los Angeles, CAl, and reported as the average ofall six readings, in kilograms. Participants with hand or wrist pain or recent hand surgery were not asked to perform this test. Bioelectric impedance (BEl) and resistance were measured with a TVI10 Body Composition Analyzer (Danninger Medical, Columbus, OH). Re-
431
sistance is proportional to total body fat. Each instrument's calibration was checked daily with a 511-ohm resistor and found to be accurate within 5.1 ohms. Impedance was measured between the right hand and right foot. Pulmonary Function Testing Participants were sitting unless they were severely overweight, as determined by a body mass index (BMI) of 35 kg/m2 or more. Spirometry was always performed first (3 to 8 FVC maneuvers), according to American Thoracic Society recommendations (10),followed by the MIP test and then (at one clinic) the MEP test. The technician always explained and demonstrated the correct maneuver first, using a spare mouthpiece. Noseclips were applied for MRP tests. A disposable cardboard mouthpiece 1 inch in diameter was firmly seated into the plastic mouthpiece adaptor for MIP tests. The participant was then instructed to exhale slowly and completely (to residual volume, RV), seal his lips firmly around the mouthpiece, and then inhale with as much force as possible "like trying to sucka thick chocolate malt through a narrow straw:' The participant was urged to "suck harder;' and then after 2 s was told "that's enough:' The participant was encouraged to look at the moving needle on the mechanical pressure gauge for feedback during each maneuver. Three to five maneuvers were done, with a goal of the highest two matching within 10%. At the end of each maneuver, the graphs of the current maneuver and previous maneuvers were color-eoded and superimposed for review by the technician (figure 1). The maximal pressure during the 2 s was calculated and displayed, and compared with the largest obtained. As many as five maneuvers were permitted in order to reach the 10% reproducibility goal. The largest value was reported. Although the MIP is actually a negative number with respect to ambient pressure, we report it here as a positive value for clarity of discussion. At one clinic (Sacramento, CAl all of the participants were then asked to perform MEP maneuvers. The cardboard mouthpiece was then replaced by a clean, large rubber mouthpiece (moulded coupler no. 022259, 1-3/8 inch ID; Warren E. Collins, Braintree, MA). The rubber mouthpiece was fitted tightly over the plastic mouthpiece adaptor. The technician demonstrated correct placement of the rubber mouthpiece held firmly against pursed lips (not inside the mouth like other mouthpieces). The participant was then coached to inhale slowly (to TLC), press the mouthpiece against his lips, and then to exhale with as much force as possible against the mouthpiece. The technician watched for leaks. The participant's cheeks were not held or stabilized, Again the goal was to obtain three to five maneuvers, the largest two matching within 10%. Processing of Results After a 5 cm H2 0 "start of test threshold" was exceeded, mouth pressure was sampled (and displayed) 10 times per second (at a resolution of 1 cm H2 0 ) for 2 s during each maneuver. All 21 pressure samples from each maneuver done were recorded/Previous investigators suggested that there could be some overshoot in the signal with some MRP instruments (13), so we also calculated the mean of the five highest MRP samples from the best maneuver. We then compared this "mean" (the pressure signal smoothed over 0.5 s) to the single highest MRP value. The difference was 5 cm H20 or less for 93% of the participants, suggesting that overshoot was minimal using our instrument, and that most of our participants maintained close to their maximal pressure for at least 0.5 s. Therefore, we report the largest value of the 21 samples obtained between 0.2 and 2.0 s of each maneuver. Statistical Analysis Univariate and bivariate relationships of anthropometric measurements, handgrip strength, bioelectric impedance, and smoking status with MIP and MEP were determined first (tables 1 to 3). Twenty-five baseline examination variables plus clinic and technician codes were then entered stepwise into multiple linear regression models with MIP or MEP as the dependent variable. The first variable considered for entry into each model was the one with the strongest correlation with the dependent variable. The probability of the F statistic was 0.05 to enter and 0.10 to remove a variable from the model; and pairwise deletion was used since left ventricular mass was missing in about one third of the cases. The stepwise
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AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Name: 246 em H20
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5 162
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4 147
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1 136 3 125
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Figure 1. Pressure was displayed in real-time on the computer monitor as shown above. Graphs started 0.2 s after a pressure threshold of 5 em H2 0 was exceeded. The current maneuver was superimposed on previous maneuvers in order for the technician to assess acceptability and reproducibility of the maneuvers. Each maneuver was color-coded by sequence number (#), and the last result was calculated, displayed, and compared with the largest previous value (%Best).
procedure was then repeated, allowing only the variables that were significant in the first model to be included, and using an F statistic of 0.001 to enter and 0.0025 to exit for the MIP model. A healthy subgroup for both MIP and MEP reference values was obtained by eliminating current smokers, those who perceived their general health to be fair or poor, and those with an FE\/, less than 65% of predicted. Multiple linear regression analysis was again performed for the "healthy" subgroup. The dependent variables MIP and MEP were modeled separately for women and men using predictor variables of age, weight, and
TABLE 1
RESULTS
ASSOCIATION OF MAXIMAL RESPIRATORY PRESSURES WITH AGE" Age Group (yrl Women 65-69 70-74 75-79 80-84 85+ Men 65-69 70-74 75-79 80-84 85+
height; their interactions, and their squared values. Cases with missing data were deleted Iistwise for this analysis. We used SPSS/PC+ Version 4.0 for all linear regression analyses. Probability density estimates were produced using Fourier series estimates (14). The estimated probability density is expressed as a Normal distribution plus terms that measure deviations from Normality. If these terms do not improve the fit, they are dropped from the equation, and the resulting estimate is the Normal distribution with mean and variance equal to the sample mean and variance. This procedure also provides a sensitive test of Normality that was used to determine if the distribution of MIP and MEP for the healthy groups differed significantly from a Normal (Gaussian) distribution.
MIP
n
%
MEP
n
%
59 56 49 45 40
1,131 888 589 243 91
38 30 20 9 3
125 121 102 84 94
176 119 85 34 13
41 28 20 8 3
84 81 74 64 56
704 728 472 253 102
31 32 21 11 5
188 179 161 142 131
113 105 59 43 9
34 32 18 13 3
" Mean MIP and MEP values for men and women in each age group are given in cm H,D. The number and percentage of participants in each age group with valid MIP or MEP results follow.
Meanmaximal respiratory pressures producedby the women were about one-third lowerthan those from the men. Meanvalueswere
TABLE 2 ASSOCIATION OF MIP AND MEP WITH GENERAL HEALTH" Response t
Codei
MIP
n
%
MEP
n
%
Excellent Very good Good Fair Poor
1 2 3 4 5
72 67 65 58 55
675 1,142 1,733 928 149
15 25 37 20 3
148 142 140 132 107
143 219 275 101 18
19 29 36 13 2
• Mean MIP and MEP values are given in cm H20. Number and percentage of participants with each responseare given. t Response to the question: "Would you say, in general, your health is.... "Those with Fair and Poor responses were eXcluded from the healthy groups defined. 1: Codes are values assigned to each response for use in regression models.
Enright, Kronmal, Manolio, et 0/.: Respiratory Muscle Strength in the Elderly TABLE 3 CORRELATES OF MIP AND MEP'
Correlations Hand grip FVC FEV, Height Weight Waist BMI Resistance Age Current smoker
MIP
MEP
0.48 0.50 0.45 0.39 0.33 0.16 0.12 -0.35 -0.20 -0.10
0.65 0.50 0.43 0.54 0.48 0.28 0.22 -0.47 -0.26 NS
Other correlations FVC and FEV, Height and weight Weight and waist Resistance and weight Resistance and waist Resistance and BMI Resistance and height
0.90 0.55 0.81 -0.66 -0.51 -0.49 -0.41
., Pearson's product-moment correlation factors are given. All correlations given were significant at p < 0.0001, using a two-tailed test.
TABLE 4 INDEPENDENT PREDICTORS OF RESPIRATORY MUSCLE STRENGTH
MIP predictors FVC Handgrip Clinic 4 Resistance Age Reactance General health Tech 11 Height Tech 10 Weight Current smoking Male sex Waist MEP predictors Male sex Handgrip Weight Age Tech 3
Mean
Cootl
SE
2.97 L 31.8 kg
+9.1 +0.69 + 15.4 -0.023 -0.44 +0.13 -1.8 +9.9 -0.54 +8.9 +0.073 -4.2 +.28 -0.19
0.61 0.052 0.84 0.0065 0.070 0.030 0.33 1.75 0.070 1.78 0.012 1.08 1.35 0.051
+21.9 + 1.7 +0.25 -1.7 + 16.6
5.76 0.28 0.066 0.33 4.99
550 ohms 72.7 yr 59.9 2.73 165
cm
71.8 kg 11.5% 93.6 cm
Definition of abbreviations: Coeff = partial regression coefficient; SE = standard error of the coefficient. • Predictors are listed in the order in which they entered each model. See the text for a list of variables that did not enter the models. All coefficients entered the model at a significance level of < 0.002; r squared for the MIP model = 0.39; for the MEP model = 0.47. Number of cases = 4.260 for the MIP model, and 685 for the MEP model.
also lower in those older than 80 yr of age compared with those 65 to 79 yr of age (table 1). Both MIP and MEP were associated with self-reported general health (table 2). Those who reported poor or fair health had considerably lower MIP and MEP values than did those who considered their health to be good, very good, or excellent. Several anthropometric variables correlated with MIP (table 3), including sex, height, weight, waist size, and age. Bioelectric resistance and reactance also correlated with these variables. FEV, and FVC (highly correlated with each other) were positively correlated with MIP (r = 0.45 and 0.50). The mean MIP/MEP of never
433
and former smokers was 66/141 cm H20 , whereas that of current smokers was 57/137 (mean MIP was 15% lower). In the multiple linear regression model of the entire cohort, male sex, FVC, handgrip strength, bioelectric reactance, and body weight were highly significant positive, independent correlates of MIP (table 4). Age, current smoking, fair or poor general health, bioelectric resistance, height and waist size were negatively correlated with MIP. When bioelectric resistance was not made available to the model, the partial regression coefficients predict a 2.2 unit increase in MIP for every 10-pound increase in body weight, and a 2.3 unit decrease in MIP for every 4-inch increase in waist size. The number of days elapsed from the beginning of the study until the test date was a significant independent correlate of MIP (p < 0.00001), with a coefficient of 0.0186, indicating an overall increase of 6.8 cm H20 during the year of baseline testing. Positive correlates of MEP in the model included grip strength, weight, younger age, and male sex. Perceived general health entered the model only if grip strength was not made available to the model. Mean MEP results from one technician (Tech 3) at the Sacramento Field Center (Clinic 4) were significantly larger than those from other technicians. Variables that did not enter models for MIP or MEP included race, pack-years of smoking, weekly alcohol intake, daily energy expenditure, diabetes, history of myocardial infarction, stroke, or other cardiovascular disease, left ventricular mass, blood pressure, use of antihypertensive drugs, ECG abnormality, creatinine, albumin, uric acid, or 2-h postload glucose or insulin levels. Healthy Group
In order to obtain a healthy subgroup from whom to derive normative equations, we eliminated current smokers (12%), the 23% who perceived their general health to be fair or poor, and those with a FEV, less than 65% of predicted (10). A history of previous smoking was not independently associated with MIP. A total of 1,602 women and 1,269 men (64.6% of the cohort) remained in the healthy group with MIP tests and 292 women and 244 men with MEP tests. There was considerable overlap in the distribution of MIP and MEP from the entire cohort and the healthy subgroup. The mean MIP values from the healthy group were 15 to 20% higher than those for the remainder of the cohort (table 5). The healthy group had significantly higher mean FVCs (p < 0.0001), lower mean bioelectric resistance (less body fat), and higher handgrip strength. Mean MEP values were 18% higher in the healthy women, but not significantly different from the remainder of the cohort for healthy men . Mean MIP results from the Sacramento clinic were significantly larger than those from the other three clinics (+ 15 cm H2 0 , 15%). None of the technicians from this clinic had significantly larger mean MIP values than other technicians, but one (Tech 3, a young man) obtained larger mean MEP values (+ 15 cm H20 ). Two technicians from the Hagerstown clinic (Techs 10 and 11, young women) obtained significantly larger mean MIP values than those of other technicians (+9 and +10 cm H2 0 ). The four MRP instruments remained trouble-free. Review of the calibration records showed that the positive and negative pressure errors of the electronic sensors remained less than 5% and did not require gain adjustments when compared with the mechanical gauges throughout the 60 wk of testing, except for an MIP gain adjustment during Week 8 at the Pittsburgh clinic. The highest MRP values from the sequence of as many as five MRP maneuvers came most frequently from the last maneuver
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Max. value occurred 40% ~-------------------------,
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unless five MEP maneuvers were done, in which case the highest value was much more likely to come from the fifth maneuver. Reference Equations
tst
2nd
ard
4th
5th
1st
2nd
Srd
4th
5th
Maneuver sequence Figure 2. Barsindicatethe percentage of the time that the highestvalue
came from each maneuver, demonstrating a learningeffect. The sum of the percentages is not100%since not all participantsperformedthe maneuverfive times.The number of participantswhodid each MIP maneuver ranges from4,872 (first) to 3,671 (last), andthe numberwho performed each MEP maneuver ranged from 794 (first) to 741 (last). (figure 2). The rate at which the maximal MIP value occurred increased with each additional maneuver done (to the maximum of five maneuvers). On the other hand, the maximal MEP value was just as likely to come from any of the first four maneuvers,
Stepwise multiple linear regression analyses determined the correlates of MIP and MEP for women and men in the healthy subgroups. Variables offered for entry into the models included only age, sex, height, and weight. The resulting reference equations are given in table 6. Second order (nonlinear) terms were not significant. Height did not enter any of the models. Results of testing the distributions for departure from normality were not significant for the healthy women, but they were skewed for MIP and MEP in healthy men. For this reason, the lower limit of the normal range (LLN) was defined as the fifth percentile of the distribution of actual minus predicted values (residuals) for the healthy group. The resulting mean lower limits of the normal ranges for our group of healthy elderly women were 26/65 cm H2 0 (MIP/MEP), whereas those for the elderly men were 44/102. Applying the reference equations derived from the healthy subset to the entire CHS cohort, 6.9% of the women and 8.8% of the men fell below the LLN for MIP. Among the subset with MEP test results (427 women and 328 men), only 6.1% of the women and 11% of the men had an abnormally low MEP (below the LLN).
DISCUSSION The primary reason for measuring maximal respiratory pressures
TABLE 5 MEAN VALUES FROM THE HEALTHY GROUP AND THE OTHERS Others
Healthy Group Mean Cases, n MIP, em H2O MEP, em H2O Age, yr Height, em Weight, kg Waist, em Grip, kg Resistance ohms FVC, L
Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men
SO
1,602 1,269 57.5 82.8 118 175 72.2 73.1 158.8 173.2 66.2 79.5 89.8 97.2 23.9 40.3 597 488 2.62 3.80
22.4 26.8 36.8 46.3 5.30 5.61 6.30 6.59 12.5 11.6 13.1 9.59 5.97 8.32 72.7 59.0 0.521 0.680
Mean 1,022 744 49.7 69.4 102 163 72.3 73.3 158.5 172.2 67.5 78.0 92.0 97.5 23.3 39.0 599 499 2.26 3.24
• The p values refer to differences between the healthy group and the other participants using a I test (NS
SO
p Value·
22.0 28.0 38.4 48.9 5.30 5.79 6.36 6.85 14.9 12.9 14.7 11.0 6.33 9.600 83.4 65.3 0.582 0.779
< 0.0001 < 0.0001 0.001 NS NS NS NS 0.003 0.01 0.Q1 < 0.0001 NS 0.02 0.003 0.05 < 0.0001 < 0.0001 < 0.0001
= not significant).
TABLE 6 REFERENCE EQUATIONS FROM THE HEAL THY GROUP
Women Men
MIP MEP MIP MEP
= (0.133 Wt) = (0.344 Wt) = (0.131 Wt) = (0.250 Wt) -
(0.805 Age) + 96 (2.12 Age) + 219 (1.27 Age) + 153 (2.95 Age) + 347
LLN"
Wt SE
Age SE
SEE
R2
Mean
Cases
-32 -52 -41 -71
0.020 0.078 0.028 0.11
0.10 0.37 0.13 0.48
21.5 33.3 25.4 42.5
0.08 0.18 0.10 0.15
57.5 118 82.8 175
1,602 359 1,269 277
Wt = weight in pounds; SE = standard error of the coefficient for that variable; SEE = standarderror of the estimate for the model. • The value given under the lowerlimit of normal (LLN) column is to be subtracted from the value determined from the reference equation in order to determine the iower limit of the normal range.
Enright, Kronmal, Manolio, et al.: Respiratory Muscle Strength in the Elderly
at the CHS baseline examination was as a potential independent predictor of cardiovascular morbidity. Weakness of the diaphragm, malnutrition, metabolic disturbances, or neuromuscular disorders will decrease both the MIP and the FVC. This respiratory change may make a person less able to withstand the stress of cardiovascular diseases. We believe that this is the first large study of maximal respiratory pressures in a representative sample of the North American population of ambulatory persons older than 65 yr of age. The largest previous study of MRP was reported more than 140 yr ago by Hutchinson, the inventor of the spirometer. He tested 1,061 men and reported mean MRPs of about 901130 cm H20 (MIP/MEP). The MIP and MEP test procedures and normative values used today by most North American pulmonary function laboratories were described by Black and Hyatt (5) in 1969.They reported much higher mean MRP values than did Hutchinson: 124/233 in 60 men 20 to 80 yr of age. The mean values for healthy elderly men in the CHS study were 83/175. Associations with Age
We found that between the ages of 65 to 85 (within the age range of those recruited into our study), the cross-sectional decreases of maximal respiratory pressure with age were between 0.8 and 2.7 cm H20 per year,with larger age-related declines in men. Black and Hyatt, who studied only 33 subjects older than 65 yr of age, found similar age-related declines in both MIP and MEP in their 55 to 80 age group (5). A more recent study of 135 adults (18 to 65 yr of age) found that age was the only significant predictor of MRP in men and height in women (4), whereas a study of 104 men and women 55 to 75 yr of age found no relationship between MRP and age (8). Like other pulmonary function parameters, mean MRPs may not change during young adulthood, as noted in a large study of 15 to 35-yr-olds (3). We are unaware of any longitudinal studies of MRPs that would indicate whether the negative association of age with respiratory muscle strength, which we have noted is merely a cohort effect or caused by the general effects of aging on skeletal muscles such as atrophy and decreased metabolic efficiency (15, 16), but we suspect the latter. There was a strong positive correlation between the FVC volume and the MIP. To the extent that the MIP reflects the strength of the respiratory muscles, both inspiratory and expiratory, this is not surprising. The limit to maximal inspiration (the upper extreme of the FVC) is reached when inspiratory muscles can no longer overcome the elastic recoil of the lung and the resistance of the chest wall to deformation. Similarly, the lower limit of the FVC (RV) is largely determined by the strength of the expiratory muscles (17). In young adults, RV occurs during exhalation when expiratory muscle strength can no longer overcome the elastic recoil of the chest wall. In older persons, it appears that RV is determined primarily by increased resistance of the airways at low lung volume. Thus, the lower limit of the FVC is dependent more on the strength of the expiratory muscles and the subject's ability to continue exhalation for a prolonged period of time, than on overcoming the elastic recoil of the chest wall. MIP primarily measures the strength of inspiratory muscles; however, since we measured MIP at RV, MIP was also affected to a lesser degree by the strength of the expiratory muscles used to reach RV prior to the maximal inspiratory effort. Sex
Our study, like previous investigations in younger age groups, found that even when many other variables related to body size
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were considered, the respiratory muscle strength of women was lower than that of men by about one-third (2-7). This is not surprising since other skeletal muscles are also generally stronger in men than in women. Whether this reduced strength translates into greater risk of pulmonary or cardiovascular disease will be determin~d by longitudinal follow-up of this cohort. Association with Body Habitus
The combination of the three variables body weight, waist size, and height, or a single bioelectric estimate of total body fat, were significantly related to respiratory muscle strength. Those with the combination of bulk (heavy weight), a small waist, and low body fat, have stronger respiratory muscles. On the other hand, a malnourished elderly man (40 pounds below the mean weight) has a 12% reduction in Mlp, and an elderly woman with a waist size of 10 inches above the mean, has an 11% reduction in MIP. As in other studies, bioelectric resistance was higher in tall subjects and in those with large abdominal girth; and (after controlling for height and waist size) increased with body weight. Bioelectric conductance, the inverse of resistance, measures the ease with which electricity passes through the body, and it is directly proportional to lean (hydrated) body mass, as confirmed by comparisons with hydrostatic weighing (18, 19). Our findings agree with previous investigators who showed that malnutrition was associated with reductions in MRP (20). Previous studies that found no difference in MRPs between morbidly obese patients and control subjects probably had too few subjects to demonstrate the effect of high body fat (21, 22). MIP and Smoking
The association of current smoking with MIP has not been previously reported. The current smokers in our study had significantly lower MIP values (10% lower), but former smoking and pack-years of smoking had no independent association with MIP. We are at a loss to explain this association. A previous study of 106 healthy adults found no effect of smoking on MIP (7). On the other hand, we found only a slight, nonsignificant association of maximal expiratory pressure and current smoking. MIP in Disease
Many diseases have been demonstrated to affect maximal respiratory pressures, including chronic obstructive lung disease (23), restrictive lung disease (low FVC with normal FE\4/FVC)(24), rheumatoid arthritis, steroid myopathy (25), neuromuscular disease, kyphoscoliosis (26), asthma hyperinflation (27), and Parkinson's disease (28). We attempted to exclude persons with these disorders from our healthy subgroup; however, we have not attempted to determine the associations of these specific diseases with maximal respiratory pressures. Quality Control
Like the FVC maneuver during spirometry, MRP maneuvers require considerable effort from the participant. The measured results are underestimated if the participant does not inhale completely (to TLC) just prior to the MEP effort, and they are slightly reduced if the participant does not exhale completely to RV just prior to the MIP effort. Submaximal effort during the subsequent 2 s while on the mouthpiece always results in lower values. A lack of enthusiastic coaching on the part of the technician will also result in lower values. We noted a strong participant learning effect during the MIP maneuvers, with the highest value most frequently coming from the fifth (and last) maneuver (figure 2). Very little learning effect
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(or fatigue) was noted during the subsequent MEP maneuvers. Others have also reported a learning effect throughout 10 MIP maneuvers (3, 22, 29). Effective demonstration of the correct maneuver by the technician before the patient tries it will allow the maximal value to be achieved earlier. In the clinical laboratory setting, it is probably reasonable to limit the number of attempts to five, as we did. Stopping after only three measurements (1), based on our data, would often result in underestimation of MIP. We believe that visual feedback and the incentive display improved participant performance. The addition of immediate calculation of the maximal value and display of reproducibility allowed the technician to coach the participant more effectively to obtain maximal results. Perhaps we should not have included dotted lines for estimated predicted values on the incentive displaystechnicians and participants may have used these as goals and thus reduced their efforts (or stopped testing) when these goals were reached. The mean MIP values actually obtained from healthy participants were very close to incentive goals for MIP (60 for women and 80 for men). However, resulting mean MEP values were about 20% larger than the MEP incentive goals (120 for women and 150 for men). There were significant intertechnician differences in mean MIP and MEP values, not reported by previous investigators. A few of our technicians obtained 8 to 12% higher values than the others. Although training and protocol were standardized, this is not an unexpected finding since the results are very dependent on the technician effectively coaching and motivating the participants. We also noted a small but significant increase in mean MIP values over the 12 months of the study. This suggests that the technicians, none of whom had ever performed MRP tests before the study started, learned how to obtain higher values with experience. It is less likely that this increase was due to instrument drift or recruitment biases. Normative Equations
Recently an American Thoracic Society (ATS)workshop discussed the characteristics of spirometry reference studies which are irn-
MIP (cmH20) 120.--------------------,
Comparison with Other Studies
Normative values for MIP and MEP for elderly men and women of average weight and height from the healthy CHS cohort generally fall between those of previous studies, when their results are extrapolated to older ages (figures 3 and 4). The MIP values from Black and Hyatt (5) and McElvaney and coworkers (8) are higher for men and women, and the values of Wilson and coworkers (4) are lower for men. The 104 subjects of McElvaney and coworkers may have been stronger since they were recruited for an exercise
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portant to ensure their validity (30). These include the following: (1) The healthy subjects should be representative of the population from which patients will be derived. (2) Subjects who are known to have lung disease, as assessed by standardized questionnaires, or to have other conditions known to adversely affect lung function should be excluded. (3) The testing and analysis methods should conform with ATS recommendations and be done by trained operators. The ATS has not published recommended standards for MRP tests; however, all of the other criteria were met by the present study, As in previous studies, the between-subject variability of MRPs was high, with less than one half of the variability explained by demographic and the many other factors that we measured. The normal range is wide, with the lower limit (fifth percentile) at 45 to 60% of the mean "predicted" value. This wide normal range reduces the value of a single MRP measurement, when compared with reference values, to detect respiratory muscle weakness. On the other hand, previous investigators have reported good withinsubject short-term repeatability of both MIP and MEP measurements, with a coefficient of variation of 7 to 10% (3, 8, 31). This improves the ability to detect a change in respiratory muscle strength in a subject after an intervention; however, our intertechnician variations suggest that the same technician should test the patient on both occasions. The CHS cohort included 129 black women and 87 black men. Because nice was not a significant factor after sex, weight, and age entered the MIP model, the reference equations may also be used for elderly black patients.
Men
40
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Figure 3. Comparison of MIP reference values. The mean (bold line) and lower limit of the normal range (LLN) (dashed line) for maximal inspiratory pressure (MIP) of elderly women ane:! men of average height and weight from the CHS study compared with healthy subjects from the previous studies of Black (5), Wilson (4), McElvaney (8), and Vincken (7).
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Enright, Kronmal, Manolio, et 01.: Respiratory Muscle Strength in the Elderly MEP (cmH20) 250,-------------------,
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Figure 4. Comparison of MEP reference values. The mean (bold line) and lower limit of the normal range (LLN) (dashed line) for maximal expiratory pressure (MEP) of elderly women and men of average height and weight from the CHS study compared with healthy subjects from previous studies (see figure 3 for references).
evaluation using newspaper advertising. On the other hand, the subjects of Black and Hyatt and of Vincken and coworkers (7) were healthy patients, including current smokers, who came to an outpatient clinic for routine annual examinations. The subjects of Wilson and coworkers were volunteers from the hospital staff, including smokers. Our MEP values are very close to those of Black and Hyatt and McElvaney and coworkers. The lower MEP values of Vincken and Wilson and their coworkers are likely due to their placement of mouthpieces inside the lips, reducing the maximal pressure that may be generated without forcing the lips away from the mouthpiece (32). Vincken and coworkers probably did not find a significant age-related factor since they studied only 10 subjects older than 65 yr of age. In conclusion, we believe that the CHS cohort is representative of elderly patients who are likely to be evaluated by physicians in the United States. We recommend that pulmonary function laboratories and respiratory therapists use the reference equations given in table 6 to define the lower limit of the normal range for MIP and MEP measurements made in patients between 65 and 85 yr of age. Acknowledgment: The writers thank Nick Bazil for writing the unique MRP software, Sheila Toogood for training the PF technicians and monitoring their quality, Dan Olson for performing the data compression, the enthusiastic CHS pulmonary function technicians, and the participants for performing these vigorous tests.
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22. FizJA, Aguilar X, CarreresA, Barbany M, FormigueraX, IzquieroJ, Morera J. Postural variation of the maximum inspiratory and expiratory pressures in obese patients. Int JObes 1991; 15:655-9. 23. Byrd RB, Hyatt RE. Maximal respiratory pressures in chronic obstructive lung disease. Am Rev Respir Dis 1968; 98:848-56. 24. DeTroyer A, Yernault JC. Inspiratory muscle force in normal subjects and patients with interstitial lung disease. Thorax 1980; 35:92-100. 25. Gorini M, Ginanni R, Spinelli A, Duranti R, Andreotti L, Scano G. Inspiratory muscle strength and respiratory drive in patients with rheumatoid arthritis. Am Rev Respir Dis 1990; 142:289-94. 26. Lisboa C, Moreno R, Fava M, Ferretti R, Cruz E. Inspiratory muscle function in patients with severe kyphoscoliosis. Am Rev Respir Dis 1985;
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419-21. 30. Becklake M, Crapo RO, Buist AS. Lung function testing: Selection of reference values and interpretative strategies. An official statement of the American Thoracic Society. Am Rev Respir Dis 1991; 144:1202-18. 31. Ng GY, Stokes MJ. Maximal inspiratory and expiratory pressures in sitting and half-lying positions in normal subjects. Respir Med 1991;
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