- Email: [email protected]
Long-Term Patterns of Obstructive Lung Disease in Cystic Fibrosis
mated for the dry aerosol. The very low deposition estimated from our data and measured by others for cromolyn may be due to the measured low quantity of active ingredient aerosolized in the respirable size range. ACKNOWLEDGMENT: The authors thank J.D. Wilson for engineering assistance, R. G. Renninger for programming aidl L. A. Higgins for art work, M. Smith for secretarial help, ana Dr. M. K. Testerman for constructive criticism. REFERENCES
1 Morrow P: Aerosol characterization and deposition. In Proceedings of the Conference on the Scientific Basis of Respiratory Therapy (Pierce AK, and Se.ltzman HA, eds). Am Rev Respir Dis 110 (part 2) : 88-99, 1974 2 Lourenco R: Aerosol therapy. In Proceedings of the Conference on the Scientific Basis of Respiratory Therapy (Pierce AK, and Saltzman HA, eds) . Am Rev Respir Dis 110 (part2):85-87, 1974 3 Mazumder MK, Kirsch J: Single particle aerodynamic relaxation time analyzer. Rev Sci lustrum 48:622-624, 1977 4 Hiller C, Mazumder M, Wilson D, et al: Aerodynamic size distribution of metered-dose bronchodilator aerosols. Am Rev Respir Dis 118:311-317, 1978 5 Lippman M: Regional deposition of particles in the human respiratory tract. In Handbook of Physiology (Lee D, ed) , Bethesda, American Physiological Society, 1977 6 Task Group on Lung Dynamics: Deposition and retention models for internal dosimetry of the human respiratory tract. Health Phys 12: 173-207, 1966 7 Hallworth GW, Andrews UG: Size analysis of suspension inhalation aerosols by inertial separation methods. J Pharm Pharmac 28:898-907, 1976 8 Moss GF, Jones KM, Ritchie JT, et al : Plasma levels and urinary excretion of disodium cromoglycate after inhalation by human volunteers. Tox Appl Pharmac 20:147-156, 1977 9 Walker SR, Evans ME, Richards AJ, et al: The fate of ac disodium cromoglycate in man. J Pharm Pharmac 42:525531, 1972
by late adolescence. Little information, however, is available about the patterns of deterioration in pulmonary function. Several investigators1 •2 found large differences in the pulmonary function among CF patients of the same age. One study, 3 a review of five to seven years of pulmonary function data, concluded that in spite of great variability, there was an exponential rate of decline. In addition, they noted that some patients had little change of function during the observation period. To identify patterns that may account for some of this variability, we analyzed pulmonary function data on a group of CF patients followed for as long as 12 years. MATERIAL AND METHODS
At the New Orleans CF Clinic, pulmonary function values have been obtained for each patient since 1965. Of 83 patients with at least three sets of values, 34 were excluded because they had less than four years of follow-up. The remaining 49 patients, 21 males and 28 females, constituted our study group. The majority of these patients hom after 1960 were diagnosed before five years of age. Pulmonary function data available for analysis included peak expiratory flows, forced vital capacity ( FVC), forced expiratory volume in 1 second ( FEV 1 ) and the percentage of the ratio of FEV1 to FVC ($ FEV/FVC). The patterns of obstructive airways disease were examined as independently as possible of lung growth, by use of the ratio of IFEV /FVC as the index of obstructive disease. Although this ratio may underestimate the actual amount of obstructive disease, it should parallel the progression of obstruction in the lungs. It, however, would be insensitive to synchronous slowing of the FEV1 and FVC, as might occur with growth retardation or in purely restrictive disease. We plotted the IFEV /FVC as a function of age for each patient. In normal subjects, this value varies little with age and, in general, remains above the 75 percent level throughout childhood and adolescence. 'lb FEV /FVC BY AGE
1
Q. (Butler): How rapidly do these particles grow? A. (Hiller) : We don't know, but our preliminary data show that growth probably occurs within milliseconds.
Long-Term Patterns of Obstrudive Lung Disease in Cystic Fibrosis*
GROUP 2 (8)
75
R. Menendez, M.D.; 0 ° F. Mather, Ph.D.; W. W. Waring, M.D., F.C.C.P. fibrosis (CF), the most common chronic deCystic structive pulmonary disease of childhood, produces
GROUP 4 <12) No Pattern
significant airways obstruction in a majority of patients
°From the Department of Pediatrics and Health Measurement Sciences, Tulane University School of Medicine, New Orleans. This study was supported in part by a Care, Teaching & Research Grant from the Cystic Fibrosis Foundation and a Pediatric Pulmonary Center Grant from the Office of Maternal and Child Health, USPHS. 00 Presently at Departments of Pediatrics and Physiology, Lovelace-Bataan Medical Center, Albuquerque.
CHEST, 77: 2, FEBRUARY, 1980 SUPPLEMENT
FIGURE I . Graphic representation of the patterns of change with age of $FEV1 /FVC in 49 CF patients. The number of patients in each group is shown in parentheses.
CHRONIC OBSTRUCTIVE LUNG DISEASE 321
EQUATIONS FOR EACH GROUP
I ~b
•GROUP 1
~
%FEV1/FVC
=
a 1 + b age
age
•I
~GROUP2 %FEV 1/
L__
FVC
=a
age
'I ~b
eGROUP 3
l( FEV1/FVC " o + b 4 (•o• ·•oobp)
age b'p
FIGURE 2. Graphic solution to the equations that describe the changes with age in %FEV /FVC. Equations 1 and 2 are special cases of equation 3. £:,. is a "switch" that turns on the linear decline phase. REsULTS AND DISCUSSION
There were basic patterns of change in %FEV1 /FVC with age. These are shown in diagram form on Figure 1. Sixteen patients in group 1 had a pattern of early linear decline beginning on or before age six. Six patients in group 2 showed a pattern of no change throughout the period of observation remaining within the normal range from as early as age six to as late as age 15. Fifteen patients in group 3 showed a pattern of no change followed by sudden linear decline. A fourth group of 12 patients showed such great variability that no pattern could be described. Since the group 3 pattern combines the features of the other two patterns, we considered it the more general model. It consisted of a period of constant tracking within the normal range ( > 75%) followed by a linear decline phase. Although group 1 patients could have had a period of normal tracking albeit very short, we would not have been able to detect it since it would have occurred before age six. Group 2 patients showed no correlation between %FEV1 /FVC and age. Simple mathematical models were used to describe the behavior of each patient with a recognizable pattern. Figure 2 shows these patterns and the equations used to describe them. For group 1 subjects, the annual rate of decline is given by the slope of the straight line equation. Group 2 subjects are each described by an estimate of their constant normal tracking value. A constant tracking value, a breakpoint age, and a slope describe the patients in group 3. These estimates summarize the pulmonary function history of each patient as given by the %FEV1 /FVC and permit comparisons of the groups. To determine whether the rate of decline in % FEV 1/FVC is the same among individuals with a breakpoint before and after six years of age, we compared the
322 22nd ASPEN LUNG CONFERENCE
slopes for groups 1 and 3. The rates of decline ranged from 1.5 percent per annum to 9.1 percent per annum in group 1, and 2.5 percent per annum to 5.8 percent per annum in group 3. Although the average rate of decline in group 3, 4.5 percent per annum, is slightly larger than group 1, 3.5 percent per annum, the difference is not statistically significant. Thus, the magnitude of the rate of decline appears to be independent of the age at which the decline begins. We found no significant sex differences in the rates of decline in any of the groups. To determine whether group 2 patients tracked at a different value from group 3 patients, we compared the intercepts of %FEV1 /FVC for these two groups. The tracking values ranged from 83 percent to 91 percent in group 2, and 73 percent to 91 percent in group 3. Group 3 patients were, on the average, 6 percentage points below group 2 and this difference was significant at the 5 percent level. However, two of the patients in group 3 who had tracking values below 75 percent were found to have entered the clinic at late ages. Because of the absence of values at early ages, these patients would tend to have overestimated breakpoint ages and underestimated tracking values. When these patients were removed, the differences between the groups was not significant. Nevertheless, there are good reasons to believe that this difference may be real, and that the tracking values of group 3 patients are lower than those of group 2. Group 3 patients are the remnants of an early cohort of individuals who may have had a somewhat different clinical experience than that of the later born members of group 2. Both groups were, however, within the "normal" range. Summary statistics on the breakpoint ages for group 3 patients are shown in Table 1. The breakpoint ages range from 9.6 to 17.6 years, within a mean of 13.4 years. Because of the absence of values before age six, no breakpoint ages can be estimated below that age. Breakpoint ages were not observed in the seven to nine year age group, probably because of the sparcity of data with which to estimate a breakpoint on or near that age. The variability in group 4-the no discernable pattern group-could have been in part due to poor single-day reproducibility. To test this hypothesis, we assessed the general single-day reproducibility of data from each patient throughout the period of observation. Reproducibility was graded as good, fair or poor. As shown on Table 2, distribution of fairly to poorly reproducible data does not appear to differ significantly from group to group. The question of how sensitive the %FEV1 / FVC is in paralleling the obstruction in the lungs is more difficult Table I --Croup 3 Breakpoint A«u
Average Standard error N
13.4 0.5 15
Minimum
9.6
Maximum
17.6
CHEST, 77: 2, FEBRUARY, 1980 SUPPLEMENT
Table 2--Aueument of Reprodllcibility
Group
Good-Fair
1 2
b,. Croup
Poor
Total
%Poor
12
4
16
25
6
0
6
0
a
14
1
15
7
4
9
3
12
25
Difference not significant, P>0.1 to answer from our data. We analyzed the pattern of FEV1 and FVC change with age among the different groups in an effort to determine if there were any discrepancies between them and the %FEV1/FVC. As expected, there was great variability among patients in the pattern of growth and decay of both the FVC and FEV ~> but in no instances did we find discrepancies. In the case of FEV ~> the patterns were as follows. In group 1 subjects, the FEV1 "grew" normally. In group 2 subjects, who had early steady decline, the FEV1 showed marked slowing throughout the observation period. For group 3 subjects, who had normal tracking followed by a breakpoint and then a steady decline, the FEV1 seemed to "grow" normally to the breakpoint age and then decline. In group 4 patients, the no pattern group, there was slowing but also a tendency to "oscillate," making the %FEV 1/ FVC impossible to model. It can he seen from these patterns that the decline in %FEV 1/ FVC cannot be adequately described by simple exponential decay models. In spite of the great variability of individual patient measurements, many CF patients may be classified into groups representing recognizable patterns, consistent with the previous observations that CF patients may have normal pulmonary function into late adolescence or they may he grossly abnormal by six years of age. There remain, however, a large number of patients who cannot he classified into the patterns described. For those in whom a pattern is established, once the deline in %FEV 1/FVC hegins, its magnitude appears to he independent of the age of onset. It seems unlikely that "normal" tracking %FEV1/FVC values represent the absence of obstructive disease. It is more likely that the opposite is true. More clinico-pathologic correlations are needed to verify this point. Factors which may affect the appearance of the patterns, in particular, the breakpoint age, are unknown and more clinico-physiologic correlations are needed to clarify this point. We also deduce from these patterns that, depending on the age at which they "break," CF patients with normal pulmonary function can he at different loci in the spectrum of CF obstructive lung disease.
REFERENCES 1 Zapletal A, Motoyama EK, Gibson LE, et al: Pulmonary mechanics in asthma and cystic fibrosis. Pediatrics, 48:6472, 1971 2 Stem RC, Boat TF, Doershuk CF, et al: Course of cystic fibrosis in 95 patients. J Pediatr 89:406-411, 1976
CHEST, 77: 2, FEBRUARY, 1980 SUPPLEMENT
3 Corey M, Levison H, Crozier D: Five to seven year course of pulmonary function in cystic fibrosis. Am Rev Resp Dis 114:1035-1092, 1976 Q. (Menkes) : Was pulmonary function deterioration associated with any particular sputum culture characteristic? A . (Menendez): This question was not evaluated. Q. (Chemiack): Is the break point in FEV1 associated with smoking or infection? A . (Menendez): We have not evaluated our data with these questions in mind.
Prevalence and Severity of Morphologic Emphysema and Bronchitis in Non-Textile and Cotton-Textile Workers* Philip C. Pratt, M.D., F.C .C.P.; Robin T. Vollmer, M.D.; ·
and ]ames A. Miller, M.D .oo
Byssinosis is a clinical syndrome defined in subjective terms beginning with "Monday morning chest tightness" and progressing, in a proportion of workers, to chronic irreversible respiratory impairment and failure.1•2 Expiratory air-flow obstruction is objectively demonstrable early and is the major mechanism of the later impairment.3 Clinical and physiologic aspects of the syndrome, and the characteristics of cotton dust (physical and chemical) have been studied extensively; physiologic responses occur within hours of exposure and probably involve smooth muscle contraction}•~ However, little has been written about the associated changes in pulmonary morphology. Possible lesions could involve airways or alveoli or both and range from causation of a specific disease, to enhancement of prevalence or severity of one or more diseases which also exist in the general population. There is no support in the literature for the concept that a specific lesion is characteristic of byssinosis.a MATERIAL, METIIODS AND REsULTS
This study has examined both the prevalence and extent of centrilobular emphysema and airway mucus secretory activity in a randomly collected series of inflation-fixed lungs obtained at autopsy from 44 cotton industry workers and 521 non-cotton workers. Extent was measured by pointcounting.7 Using hospital medical records the cases have been divided into non-smokers ( 105), cigarette smokers ( 427), and pipe-cigar smokers ( 33) . Statistical analysis involved t-tests and the non-parametric Wilcoxon rank order test. Statistically significant differences in both preva0From the Departments of Pathology, Veterans Administration and the Duke University Medical Centers Durham North Carolina. ' , 00 Presently at Department of Pathology Candler Genral Hospital, Savannah, Georgia. ' Reprint requests: Dr. Pratt1 Department of Pathologu Btn:
3712, IJuk$ University Meaical Center, Durham 27710'
CHRONIC OBSTRUCTIVE LUNG DISEASE 323
1 Morrow P: Aerosol characterization and deposition. In Proceedings of the Conference on the Scientific Basis of Respiratory Therapy (Pierce AK, and Se.ltzman HA, eds). Am Rev Respir Dis 110 (part 2) : 88-99, 1974 2 Lourenco R: Aerosol therapy. In Proceedings of the Conference on the Scientific Basis of Respiratory Therapy (Pierce AK, and Saltzman HA, eds) . Am Rev Respir Dis 110 (part2):85-87, 1974 3 Mazumder MK, Kirsch J: Single particle aerodynamic relaxation time analyzer. Rev Sci lustrum 48:622-624, 1977 4 Hiller C, Mazumder M, Wilson D, et al: Aerodynamic size distribution of metered-dose bronchodilator aerosols. Am Rev Respir Dis 118:311-317, 1978 5 Lippman M: Regional deposition of particles in the human respiratory tract. In Handbook of Physiology (Lee D, ed) , Bethesda, American Physiological Society, 1977 6 Task Group on Lung Dynamics: Deposition and retention models for internal dosimetry of the human respiratory tract. Health Phys 12: 173-207, 1966 7 Hallworth GW, Andrews UG: Size analysis of suspension inhalation aerosols by inertial separation methods. J Pharm Pharmac 28:898-907, 1976 8 Moss GF, Jones KM, Ritchie JT, et al : Plasma levels and urinary excretion of disodium cromoglycate after inhalation by human volunteers. Tox Appl Pharmac 20:147-156, 1977 9 Walker SR, Evans ME, Richards AJ, et al: The fate of ac disodium cromoglycate in man. J Pharm Pharmac 42:525531, 1972
by late adolescence. Little information, however, is available about the patterns of deterioration in pulmonary function. Several investigators1 •2 found large differences in the pulmonary function among CF patients of the same age. One study, 3 a review of five to seven years of pulmonary function data, concluded that in spite of great variability, there was an exponential rate of decline. In addition, they noted that some patients had little change of function during the observation period. To identify patterns that may account for some of this variability, we analyzed pulmonary function data on a group of CF patients followed for as long as 12 years. MATERIAL AND METHODS
At the New Orleans CF Clinic, pulmonary function values have been obtained for each patient since 1965. Of 83 patients with at least three sets of values, 34 were excluded because they had less than four years of follow-up. The remaining 49 patients, 21 males and 28 females, constituted our study group. The majority of these patients hom after 1960 were diagnosed before five years of age. Pulmonary function data available for analysis included peak expiratory flows, forced vital capacity ( FVC), forced expiratory volume in 1 second ( FEV 1 ) and the percentage of the ratio of FEV1 to FVC ($ FEV/FVC). The patterns of obstructive airways disease were examined as independently as possible of lung growth, by use of the ratio of IFEV /FVC as the index of obstructive disease. Although this ratio may underestimate the actual amount of obstructive disease, it should parallel the progression of obstruction in the lungs. It, however, would be insensitive to synchronous slowing of the FEV1 and FVC, as might occur with growth retardation or in purely restrictive disease. We plotted the IFEV /FVC as a function of age for each patient. In normal subjects, this value varies little with age and, in general, remains above the 75 percent level throughout childhood and adolescence. 'lb FEV /FVC BY AGE
1
Q. (Butler): How rapidly do these particles grow? A. (Hiller) : We don't know, but our preliminary data show that growth probably occurs within milliseconds.
Long-Term Patterns of Obstrudive Lung Disease in Cystic Fibrosis*
GROUP 2 (8)
75
R. Menendez, M.D.; 0 ° F. Mather, Ph.D.; W. W. Waring, M.D., F.C.C.P. fibrosis (CF), the most common chronic deCystic structive pulmonary disease of childhood, produces
GROUP 4 <12) No Pattern
significant airways obstruction in a majority of patients
°From the Department of Pediatrics and Health Measurement Sciences, Tulane University School of Medicine, New Orleans. This study was supported in part by a Care, Teaching & Research Grant from the Cystic Fibrosis Foundation and a Pediatric Pulmonary Center Grant from the Office of Maternal and Child Health, USPHS. 00 Presently at Departments of Pediatrics and Physiology, Lovelace-Bataan Medical Center, Albuquerque.
CHEST, 77: 2, FEBRUARY, 1980 SUPPLEMENT
FIGURE I . Graphic representation of the patterns of change with age of $FEV1 /FVC in 49 CF patients. The number of patients in each group is shown in parentheses.
CHRONIC OBSTRUCTIVE LUNG DISEASE 321
EQUATIONS FOR EACH GROUP
I ~b
•GROUP 1
~
%FEV1/FVC
=
a 1 + b age
age
•I
~GROUP2 %FEV 1/
L__
FVC
=a
age
'I ~b
eGROUP 3
l( FEV1/FVC " o + b 4 (•o• ·•oobp)
age b'p
FIGURE 2. Graphic solution to the equations that describe the changes with age in %FEV /FVC. Equations 1 and 2 are special cases of equation 3. £:,. is a "switch" that turns on the linear decline phase. REsULTS AND DISCUSSION
There were basic patterns of change in %FEV1 /FVC with age. These are shown in diagram form on Figure 1. Sixteen patients in group 1 had a pattern of early linear decline beginning on or before age six. Six patients in group 2 showed a pattern of no change throughout the period of observation remaining within the normal range from as early as age six to as late as age 15. Fifteen patients in group 3 showed a pattern of no change followed by sudden linear decline. A fourth group of 12 patients showed such great variability that no pattern could be described. Since the group 3 pattern combines the features of the other two patterns, we considered it the more general model. It consisted of a period of constant tracking within the normal range ( > 75%) followed by a linear decline phase. Although group 1 patients could have had a period of normal tracking albeit very short, we would not have been able to detect it since it would have occurred before age six. Group 2 patients showed no correlation between %FEV1 /FVC and age. Simple mathematical models were used to describe the behavior of each patient with a recognizable pattern. Figure 2 shows these patterns and the equations used to describe them. For group 1 subjects, the annual rate of decline is given by the slope of the straight line equation. Group 2 subjects are each described by an estimate of their constant normal tracking value. A constant tracking value, a breakpoint age, and a slope describe the patients in group 3. These estimates summarize the pulmonary function history of each patient as given by the %FEV1 /FVC and permit comparisons of the groups. To determine whether the rate of decline in % FEV 1/FVC is the same among individuals with a breakpoint before and after six years of age, we compared the
322 22nd ASPEN LUNG CONFERENCE
slopes for groups 1 and 3. The rates of decline ranged from 1.5 percent per annum to 9.1 percent per annum in group 1, and 2.5 percent per annum to 5.8 percent per annum in group 3. Although the average rate of decline in group 3, 4.5 percent per annum, is slightly larger than group 1, 3.5 percent per annum, the difference is not statistically significant. Thus, the magnitude of the rate of decline appears to be independent of the age at which the decline begins. We found no significant sex differences in the rates of decline in any of the groups. To determine whether group 2 patients tracked at a different value from group 3 patients, we compared the intercepts of %FEV1 /FVC for these two groups. The tracking values ranged from 83 percent to 91 percent in group 2, and 73 percent to 91 percent in group 3. Group 3 patients were, on the average, 6 percentage points below group 2 and this difference was significant at the 5 percent level. However, two of the patients in group 3 who had tracking values below 75 percent were found to have entered the clinic at late ages. Because of the absence of values at early ages, these patients would tend to have overestimated breakpoint ages and underestimated tracking values. When these patients were removed, the differences between the groups was not significant. Nevertheless, there are good reasons to believe that this difference may be real, and that the tracking values of group 3 patients are lower than those of group 2. Group 3 patients are the remnants of an early cohort of individuals who may have had a somewhat different clinical experience than that of the later born members of group 2. Both groups were, however, within the "normal" range. Summary statistics on the breakpoint ages for group 3 patients are shown in Table 1. The breakpoint ages range from 9.6 to 17.6 years, within a mean of 13.4 years. Because of the absence of values before age six, no breakpoint ages can be estimated below that age. Breakpoint ages were not observed in the seven to nine year age group, probably because of the sparcity of data with which to estimate a breakpoint on or near that age. The variability in group 4-the no discernable pattern group-could have been in part due to poor single-day reproducibility. To test this hypothesis, we assessed the general single-day reproducibility of data from each patient throughout the period of observation. Reproducibility was graded as good, fair or poor. As shown on Table 2, distribution of fairly to poorly reproducible data does not appear to differ significantly from group to group. The question of how sensitive the %FEV1 / FVC is in paralleling the obstruction in the lungs is more difficult Table I --Croup 3 Breakpoint A«u
Average Standard error N
13.4 0.5 15
Minimum
9.6
Maximum
17.6
CHEST, 77: 2, FEBRUARY, 1980 SUPPLEMENT
Table 2--Aueument of Reprodllcibility
Group
Good-Fair
1 2
b,. Croup
Poor
Total
%Poor
12
4
16
25
6
0
6
0
a
14
1
15
7
4
9
3
12
25
Difference not significant, P>0.1 to answer from our data. We analyzed the pattern of FEV1 and FVC change with age among the different groups in an effort to determine if there were any discrepancies between them and the %FEV1/FVC. As expected, there was great variability among patients in the pattern of growth and decay of both the FVC and FEV ~> but in no instances did we find discrepancies. In the case of FEV ~> the patterns were as follows. In group 1 subjects, the FEV1 "grew" normally. In group 2 subjects, who had early steady decline, the FEV1 showed marked slowing throughout the observation period. For group 3 subjects, who had normal tracking followed by a breakpoint and then a steady decline, the FEV1 seemed to "grow" normally to the breakpoint age and then decline. In group 4 patients, the no pattern group, there was slowing but also a tendency to "oscillate," making the %FEV 1/ FVC impossible to model. It can he seen from these patterns that the decline in %FEV 1/ FVC cannot be adequately described by simple exponential decay models. In spite of the great variability of individual patient measurements, many CF patients may be classified into groups representing recognizable patterns, consistent with the previous observations that CF patients may have normal pulmonary function into late adolescence or they may he grossly abnormal by six years of age. There remain, however, a large number of patients who cannot he classified into the patterns described. For those in whom a pattern is established, once the deline in %FEV 1/FVC hegins, its magnitude appears to he independent of the age of onset. It seems unlikely that "normal" tracking %FEV1/FVC values represent the absence of obstructive disease. It is more likely that the opposite is true. More clinico-pathologic correlations are needed to verify this point. Factors which may affect the appearance of the patterns, in particular, the breakpoint age, are unknown and more clinico-physiologic correlations are needed to clarify this point. We also deduce from these patterns that, depending on the age at which they "break," CF patients with normal pulmonary function can he at different loci in the spectrum of CF obstructive lung disease.
REFERENCES 1 Zapletal A, Motoyama EK, Gibson LE, et al: Pulmonary mechanics in asthma and cystic fibrosis. Pediatrics, 48:6472, 1971 2 Stem RC, Boat TF, Doershuk CF, et al: Course of cystic fibrosis in 95 patients. J Pediatr 89:406-411, 1976
CHEST, 77: 2, FEBRUARY, 1980 SUPPLEMENT
3 Corey M, Levison H, Crozier D: Five to seven year course of pulmonary function in cystic fibrosis. Am Rev Resp Dis 114:1035-1092, 1976 Q. (Menkes) : Was pulmonary function deterioration associated with any particular sputum culture characteristic? A . (Menendez): This question was not evaluated. Q. (Chemiack): Is the break point in FEV1 associated with smoking or infection? A . (Menendez): We have not evaluated our data with these questions in mind.
Prevalence and Severity of Morphologic Emphysema and Bronchitis in Non-Textile and Cotton-Textile Workers* Philip C. Pratt, M.D., F.C .C.P.; Robin T. Vollmer, M.D.; ·
and ]ames A. Miller, M.D .oo
Byssinosis is a clinical syndrome defined in subjective terms beginning with "Monday morning chest tightness" and progressing, in a proportion of workers, to chronic irreversible respiratory impairment and failure.1•2 Expiratory air-flow obstruction is objectively demonstrable early and is the major mechanism of the later impairment.3 Clinical and physiologic aspects of the syndrome, and the characteristics of cotton dust (physical and chemical) have been studied extensively; physiologic responses occur within hours of exposure and probably involve smooth muscle contraction}•~ However, little has been written about the associated changes in pulmonary morphology. Possible lesions could involve airways or alveoli or both and range from causation of a specific disease, to enhancement of prevalence or severity of one or more diseases which also exist in the general population. There is no support in the literature for the concept that a specific lesion is characteristic of byssinosis.a MATERIAL, METIIODS AND REsULTS
This study has examined both the prevalence and extent of centrilobular emphysema and airway mucus secretory activity in a randomly collected series of inflation-fixed lungs obtained at autopsy from 44 cotton industry workers and 521 non-cotton workers. Extent was measured by pointcounting.7 Using hospital medical records the cases have been divided into non-smokers ( 105), cigarette smokers ( 427), and pipe-cigar smokers ( 33) . Statistical analysis involved t-tests and the non-parametric Wilcoxon rank order test. Statistically significant differences in both preva0From the Departments of Pathology, Veterans Administration and the Duke University Medical Centers Durham North Carolina. ' , 00 Presently at Department of Pathology Candler Genral Hospital, Savannah, Georgia. ' Reprint requests: Dr. Pratt1 Department of Pathologu Btn:
3712, IJuk$ University Meaical Center, Durham 27710'
CHRONIC OBSTRUCTIVE LUNG DISEASE 323