Original Papers © 1991 S. Karger AG. Basel 0253-5068/91/0092-0070S2.75/0
Blood Purif 1991:9:70-73
Bronchial Reactivity in Patients Undergoing Long-Term Haemodialysis for Chronic Renal Failure M.J. Walshaw, R. Lim. R. Ahmad, C.R.K. Hind Department of Medicine. Royal Liverpool Hospital. University of Liverpool, UK
Key Words. Asthma • Bronchial hyper-reactivity • Neutrophil sequestration • Haemodialysis
Introduction Several disturbances of respiratory func tion occur during haemodialysis, which are thought to account for the hypoxaemia that develops using cuprophane dialysers [1], These include changes in minute ventilation [2], tidal volume [3] and defects in gas ex change at the alveolar-capillary membrane [4]The observation that occasional patients develop asthmatic symptoms during haemo dialysis [5] has focussed interest on changes in airway function. Recent studies from this
unit reported small but significant falls in peak expiratory flow rate in most patients undergoing haemodialysis for chronic renal failure [6], especially in those using a new cuprophane dialyser [7], The mechanisms of these changes in airway function are un known. One suggestion is that they arise as a result of the neutrophil trapping and activa tion which is known to occur within the alveolar and bronchial circulation during by pass procedures [8. 9], and can result in parenchymal and bronchial inflammation [10]. Similar findings of sequestrated neutro phils within the bronchial mucosa are thought
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/22/2018 5:48:04 PM
Abstract. Trapping of neutrophils within the lung occurs in patients undergoing haemo dialysis and is also a possible mechanism in the pathogenesis of bronchial hyper-responsiveness. Falls in peak expiratory flow rate occur in most dialysis patients, and some develop overt asthmatic symptoms. To see whether these changes in airway function are secondary to increases in bronchial reactivity during haemodialysis, we therefore performed histamine challenge testing in 6 non-asthmatic patients before and after haemodialysis. No change in reactivity was observed, suggesting that haemodialysis does not commonly result in bron chial hyper-reactivity in non-asthmatic individuals.
71
Bronchial Reactivity in Patients on Haemodialysis
to underlie the bronchial hvper-responsiveness induced by ozone and allergen in dogs [11]. One possible explanation for the mech anism of the reversible airway obstruction documented in haemodialysis patients, there fore. is that there is a transient bronchial hy per-responsiveness induced by the procedure. To investigate this possibility further we performed histamine challenge tests in pa tients undergoing haemodialysis for endstage chronic renal failure to determine whether any change in bronchial responsive ness occurred after dialysis.
Patients and Methods Patients
Methods A standard histamine challenge test was carried out on the day before dialysis and then immediately (always within 1 h) following dialysis. Both tests were carried out at the same time of day. The provocation concentration of histamine which caused a 20% fall in FEV, (the PCi0) was taken as an index of bronchial reactivity. In addition, peak flow rate was measured by a physiological measurement technician before di alysis and then half-hourly throughout the procedure which lasted for 4 h in all cases. The results were sub jected to analysis using the two-tailed Wilcoxon signed-rank sum test; statistical significance was con sidered to be achieved at the 5% level.
Fig. 1. PC m before and after haemodialysis (n = 6). o = New membrane; • = re-used membrane.
Results One patient did not respond to histamine (even at the highest dose of 64 mg/ml) both before and after dialysis. All the remaining patients had predialysis PC 20S which fell within the normal range for our laboratory (> 4 mg/ml) [12], Although there was some variation in PCto following dialysis, this did not reach significance (pre-dialysis PC20: mean 28.4 mg/ml. range 5.2-64.0; post-dial ysis PCyo: mean 31.3 mg/ml. range 10.664.0). The 2 patients who used fresh dialysis membranes showed no trend in PC20 follow ing dialysis (fig. 1).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/22/2018 5:48:04 PM
Six patients (4 male. 2 female; mean age 51 years, range 41-64) underoing long-term hospital haemodi alysis for chronic renal failure using cuprophane dialyser membranes formed the study population. All patients gave informed consent. There were 3 smok ers and I ex-smoker. As a group they did not have resting airway obstruction (mean FEVt/FVC 81%. range 78-87). No patient gave a history suggestive of asthma and none were taking anti-histamines or bronchodilators during the study period, nor any other medication known to interfere with bronchial reactiv ity (e.g. angiotensin-converting enzyme inhibitors). Five patients were habitually re-using their cupro phane dialyser membranes.
Walshaw/Lim/Ahmad/Hind
72
Table I. Mean peak expiratory flow rate (PEFR) during dialysis (n = 6) Dialysis time, h
Mean fall (%)
Mean SD
0.5
1
1.5
2
2.5
3
3.5
4
429 69
426 84 0.7
406 65
423 108 1.4
413 101 3.8
419 103 2.4
416 102 3.1
411 106 4.2
412 83 4.0
-
5.4
There was a small and sustained fall in mean peak flow rate after the initiation of dialysis, but this never exceeded 4% and was not a statistically significant decrease (ta ble 1).
Discussion The group of non-asthmatic patients in this study did not show a change in bronchial reactivity following haemodialysis, nor as a group did they exhibit bronchial hyper-reac tivity. These results suggest that the dialysis procedure per se does not commonly result in any change in bronchial hyper-reponsiveness in this stable group of end-stage renal failure patients. Of course, the pulmonary neutrophil sequestration during haemodialy sis does occur early, and plasma neutrophil levels rise quickly following this [8, 13]. It may well be that any neutrophil infiltration of the bronchial mucosa is only transient and the bronchial hyper-reactivity so produced (if this is the mechanism) is too fleeting to be documented by a histamine challenge test performed after the procedure. Against this explanation are the observations in animal models that induced bronchial hyper-re sponsiveness persists for longer than the 4 h
for dialysis in this study [11]. Several of our patients were smokers, a condition also asso ciated with increased numbers of bronchial neutrophils [14], However, the normal PC20 observed before dialysis suggests that this factor is not playing a role in these pa tients. In the patients studied here there was no significant change in peak flow rate at any stage of the dialysis, suggesting that there was no alteration in airway calibre during the procedure. A small but significant fall in peak flow rate was described in the recent study of Davenport and Williams [6]. How ever. their patients were probably less stable during dialysis and it is possible that the increased lung water described during this procedure could account for their findings. Our patients all had stable chronic renal fail ure and underwent uncomplicated dialysis as witnessed by no change in weight during the procedure, and the results are in keeping with other more recent studies on peak flow measurements during haemodialysis [15]. Acknowledgements We are grateful to Mrs B. Lea and her technicians in the Physiological Measurement Laboratory for ex pert assistance throughout the study.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/22/2018 5:48:04 PM
PEFR. 1/min
pre
Bronchial Reactivity in Patients on Haemodialysis
1 Burns C, Schcinhorn D: Hvpoxaemia during hae modialysis. Arch Intern Med 1982; 142:1350— 1353. 2 Aurigemma NM, Feldman NT. Gottlieb M. In gram RH. Lazarus JM. Lowric EG: Arterial oxy genation during haemodialysis. N Engl J Med 1977;297:871-873. 3 DcBacker WA. Verpooten GA. Borgonjon DJ, Vermiere PA, Lins RL, DeBroe ME: Hvpoxaemia during haemodialysis: Effects of different mem branes and dialysate compositions. Kidney Int 1983;23:738-743. 4 Graf V. Stummvoll HK. Haber P. Kovarik J: Pathophysiology of dialysis related hypoxaemia. Proc EDTA 1980;17:155-161. 5 Aljama P. Brown P. Turner P, Ward MK. Kerr DNS: Haemodialysis triggered asthma. Br Med J 1978:3:251-252. ' 6 Davenport A, Williams AJ: Fall in peak flow rate during haemodialysis in patients with chronic re nal failure. Thorax 1988:43:693-696. 7 Davenport A. Ahmad R: The effect of reuse of cuprophanc dialyzers on dialysis-induced leuko penia and thrombocytopenia. Dial Transplant 1988:17:132-134. 8 Craddock PR. Fehr J. Dalmasso AP. Brigham KL, Jacob HS: Haemodialysis leucopenia. J Clin In vest 1977:59:879-888. 9 Hammerschmidt DE. Stroncek DF. Bowers TK. et al: Complement activation and neutropenia oc curring during cardiopulmonary bypass. .1 Thorac Cardiovasc Surg 1981;81:370-377.
10 Ratcliff NB. Young WG, Hackel DB. Mikat E, Wilson JW: Pulmonary injury secondary to extra corporeal circulation. J Thorac Cardiovasc Surg 1973:65:425-432. 11 Barnes PJ: New concepts in the pathogenesis of bronchial hyperresponsiveness and asthma. J Al lergy Clin Immunol 1989:83:1013-1026. 12 Walshaw MJ: Bronchial reactivity: Its assessment by the histamine challenge test. Breath 1984;21: 11-13. I 3 Walker JF. Lindsay RM, Sibbald JW. Linton AL: Acute pulmonary hypertension, leucopenia and hypoxia in early haemodialysis. Proc EDTA 1984; 21:135-142. 14 Kilburn KH. McKenzie W: Leucocyte recruit ment to airways by cigarette smoke and particle phase in contrast to cytotoxicity of vapor. Science 1975;189:634-636. 15 Wu PG. Cheng IKP. Lam WK: Fall in peak expi ratory flow rate during haemodialysis in patients with ehronic renal failure (letter). Thorax 1990; 45:78.
Accepted: October 31,1990 C.R.K. Hind. MD. MRCP Consultant Chest Physician Department of Medicine Royal Liverpool Hospital University of Liverpool Liverpool 1.7 8XP (UK)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/22/2018 5:48:04 PM
References
73
Blood Purif 1991:9:70-73
Bronchial Reactivity in Patients Undergoing Long-Term Haemodialysis for Chronic Renal Failure M.J. Walshaw, R. Lim. R. Ahmad, C.R.K. Hind Department of Medicine. Royal Liverpool Hospital. University of Liverpool, UK
Key Words. Asthma • Bronchial hyper-reactivity • Neutrophil sequestration • Haemodialysis
Introduction Several disturbances of respiratory func tion occur during haemodialysis, which are thought to account for the hypoxaemia that develops using cuprophane dialysers [1], These include changes in minute ventilation [2], tidal volume [3] and defects in gas ex change at the alveolar-capillary membrane [4]The observation that occasional patients develop asthmatic symptoms during haemo dialysis [5] has focussed interest on changes in airway function. Recent studies from this
unit reported small but significant falls in peak expiratory flow rate in most patients undergoing haemodialysis for chronic renal failure [6], especially in those using a new cuprophane dialyser [7], The mechanisms of these changes in airway function are un known. One suggestion is that they arise as a result of the neutrophil trapping and activa tion which is known to occur within the alveolar and bronchial circulation during by pass procedures [8. 9], and can result in parenchymal and bronchial inflammation [10]. Similar findings of sequestrated neutro phils within the bronchial mucosa are thought
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/22/2018 5:48:04 PM
Abstract. Trapping of neutrophils within the lung occurs in patients undergoing haemo dialysis and is also a possible mechanism in the pathogenesis of bronchial hyper-responsiveness. Falls in peak expiratory flow rate occur in most dialysis patients, and some develop overt asthmatic symptoms. To see whether these changes in airway function are secondary to increases in bronchial reactivity during haemodialysis, we therefore performed histamine challenge testing in 6 non-asthmatic patients before and after haemodialysis. No change in reactivity was observed, suggesting that haemodialysis does not commonly result in bron chial hyper-reactivity in non-asthmatic individuals.
71
Bronchial Reactivity in Patients on Haemodialysis
to underlie the bronchial hvper-responsiveness induced by ozone and allergen in dogs [11]. One possible explanation for the mech anism of the reversible airway obstruction documented in haemodialysis patients, there fore. is that there is a transient bronchial hy per-responsiveness induced by the procedure. To investigate this possibility further we performed histamine challenge tests in pa tients undergoing haemodialysis for endstage chronic renal failure to determine whether any change in bronchial responsive ness occurred after dialysis.
Patients and Methods Patients
Methods A standard histamine challenge test was carried out on the day before dialysis and then immediately (always within 1 h) following dialysis. Both tests were carried out at the same time of day. The provocation concentration of histamine which caused a 20% fall in FEV, (the PCi0) was taken as an index of bronchial reactivity. In addition, peak flow rate was measured by a physiological measurement technician before di alysis and then half-hourly throughout the procedure which lasted for 4 h in all cases. The results were sub jected to analysis using the two-tailed Wilcoxon signed-rank sum test; statistical significance was con sidered to be achieved at the 5% level.
Fig. 1. PC m before and after haemodialysis (n = 6). o = New membrane; • = re-used membrane.
Results One patient did not respond to histamine (even at the highest dose of 64 mg/ml) both before and after dialysis. All the remaining patients had predialysis PC 20S which fell within the normal range for our laboratory (> 4 mg/ml) [12], Although there was some variation in PCto following dialysis, this did not reach significance (pre-dialysis PC20: mean 28.4 mg/ml. range 5.2-64.0; post-dial ysis PCyo: mean 31.3 mg/ml. range 10.664.0). The 2 patients who used fresh dialysis membranes showed no trend in PC20 follow ing dialysis (fig. 1).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/22/2018 5:48:04 PM
Six patients (4 male. 2 female; mean age 51 years, range 41-64) underoing long-term hospital haemodi alysis for chronic renal failure using cuprophane dialyser membranes formed the study population. All patients gave informed consent. There were 3 smok ers and I ex-smoker. As a group they did not have resting airway obstruction (mean FEVt/FVC 81%. range 78-87). No patient gave a history suggestive of asthma and none were taking anti-histamines or bronchodilators during the study period, nor any other medication known to interfere with bronchial reactiv ity (e.g. angiotensin-converting enzyme inhibitors). Five patients were habitually re-using their cupro phane dialyser membranes.
Walshaw/Lim/Ahmad/Hind
72
Table I. Mean peak expiratory flow rate (PEFR) during dialysis (n = 6) Dialysis time, h
Mean fall (%)
Mean SD
0.5
1
1.5
2
2.5
3
3.5
4
429 69
426 84 0.7
406 65
423 108 1.4
413 101 3.8
419 103 2.4
416 102 3.1
411 106 4.2
412 83 4.0
-
5.4
There was a small and sustained fall in mean peak flow rate after the initiation of dialysis, but this never exceeded 4% and was not a statistically significant decrease (ta ble 1).
Discussion The group of non-asthmatic patients in this study did not show a change in bronchial reactivity following haemodialysis, nor as a group did they exhibit bronchial hyper-reac tivity. These results suggest that the dialysis procedure per se does not commonly result in any change in bronchial hyper-reponsiveness in this stable group of end-stage renal failure patients. Of course, the pulmonary neutrophil sequestration during haemodialy sis does occur early, and plasma neutrophil levels rise quickly following this [8, 13]. It may well be that any neutrophil infiltration of the bronchial mucosa is only transient and the bronchial hyper-reactivity so produced (if this is the mechanism) is too fleeting to be documented by a histamine challenge test performed after the procedure. Against this explanation are the observations in animal models that induced bronchial hyper-re sponsiveness persists for longer than the 4 h
for dialysis in this study [11]. Several of our patients were smokers, a condition also asso ciated with increased numbers of bronchial neutrophils [14], However, the normal PC20 observed before dialysis suggests that this factor is not playing a role in these pa tients. In the patients studied here there was no significant change in peak flow rate at any stage of the dialysis, suggesting that there was no alteration in airway calibre during the procedure. A small but significant fall in peak flow rate was described in the recent study of Davenport and Williams [6]. How ever. their patients were probably less stable during dialysis and it is possible that the increased lung water described during this procedure could account for their findings. Our patients all had stable chronic renal fail ure and underwent uncomplicated dialysis as witnessed by no change in weight during the procedure, and the results are in keeping with other more recent studies on peak flow measurements during haemodialysis [15]. Acknowledgements We are grateful to Mrs B. Lea and her technicians in the Physiological Measurement Laboratory for ex pert assistance throughout the study.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/22/2018 5:48:04 PM
PEFR. 1/min
pre
Bronchial Reactivity in Patients on Haemodialysis
1 Burns C, Schcinhorn D: Hvpoxaemia during hae modialysis. Arch Intern Med 1982; 142:1350— 1353. 2 Aurigemma NM, Feldman NT. Gottlieb M. In gram RH. Lazarus JM. Lowric EG: Arterial oxy genation during haemodialysis. N Engl J Med 1977;297:871-873. 3 DcBacker WA. Verpooten GA. Borgonjon DJ, Vermiere PA, Lins RL, DeBroe ME: Hvpoxaemia during haemodialysis: Effects of different mem branes and dialysate compositions. Kidney Int 1983;23:738-743. 4 Graf V. Stummvoll HK. Haber P. Kovarik J: Pathophysiology of dialysis related hypoxaemia. Proc EDTA 1980;17:155-161. 5 Aljama P. Brown P. Turner P, Ward MK. Kerr DNS: Haemodialysis triggered asthma. Br Med J 1978:3:251-252. ' 6 Davenport A, Williams AJ: Fall in peak flow rate during haemodialysis in patients with chronic re nal failure. Thorax 1988:43:693-696. 7 Davenport A. Ahmad R: The effect of reuse of cuprophanc dialyzers on dialysis-induced leuko penia and thrombocytopenia. Dial Transplant 1988:17:132-134. 8 Craddock PR. Fehr J. Dalmasso AP. Brigham KL, Jacob HS: Haemodialysis leucopenia. J Clin In vest 1977:59:879-888. 9 Hammerschmidt DE. Stroncek DF. Bowers TK. et al: Complement activation and neutropenia oc curring during cardiopulmonary bypass. .1 Thorac Cardiovasc Surg 1981;81:370-377.
10 Ratcliff NB. Young WG, Hackel DB. Mikat E, Wilson JW: Pulmonary injury secondary to extra corporeal circulation. J Thorac Cardiovasc Surg 1973:65:425-432. 11 Barnes PJ: New concepts in the pathogenesis of bronchial hyperresponsiveness and asthma. J Al lergy Clin Immunol 1989:83:1013-1026. 12 Walshaw MJ: Bronchial reactivity: Its assessment by the histamine challenge test. Breath 1984;21: 11-13. I 3 Walker JF. Lindsay RM, Sibbald JW. Linton AL: Acute pulmonary hypertension, leucopenia and hypoxia in early haemodialysis. Proc EDTA 1984; 21:135-142. 14 Kilburn KH. McKenzie W: Leucocyte recruit ment to airways by cigarette smoke and particle phase in contrast to cytotoxicity of vapor. Science 1975;189:634-636. 15 Wu PG. Cheng IKP. Lam WK: Fall in peak expi ratory flow rate during haemodialysis in patients with ehronic renal failure (letter). Thorax 1990; 45:78.
Accepted: October 31,1990 C.R.K. Hind. MD. MRCP Consultant Chest Physician Department of Medicine Royal Liverpool Hospital University of Liverpool Liverpool 1.7 8XP (UK)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/22/2018 5:48:04 PM
References
73
