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(Chest. 2002;122:1988-1993.)
© 2002 American College of Chest Physicians

Vocal Cord Dysfunction Induced by Methacholine Challenge Testing*

Patrick J. Perkins, MAJ MC, USA, MD and Michael J. Morris, LTC MC, USA, MD

* From the Pulmonary Disease/Critical Care Service, Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, TX.

Correspondence to: MAJ Patrick Perkins (MCHE-MDP), Pulmonary Disease/Critical Care Service, Brooke Army Medical Center, 3851 Roger Brooke Dr, Fort Sam Houston, TX 78234-6200; e-mail: Patrick.Perkins{at}cen.amedd.army.mil


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: To determine whether methacholine challenge testing (MCT) provokes vocal cord dysfunction (VCD), as evidenced by inspiratory vocal cord closure on direct laryngoscopy, and whether spirometry and flow-volume loops (FVLs) demonstrate any changes that are suggestive of VCD.

Design: Prospective, controlled study.

Setting: Army medical center.

Patients: Thirty-four subjects all with normal baseline spirometry. Ten subjects had documented evidence of VCD, 12 subjects had exercise-induced asthma (EIA) and reactive MCT, and 12 subjects served as healthy asymptomatic control subjects.

Methods: Measurement of spirometry with FVLs and direct laryngoscopy of the vocal cords performed immediately before and after subjects had undergone MCT.

Results: Evidence of inspiratory vocal cord adduction was found in four VCD patients. Two patients had adducted vocal cords at baseline, and their conditions were unchanged after undergoing MCT. Two other patients had normal conditions at baseline and demonstrated acute inspiratory vocal cord adduction after undergoing MCT. None of the patients in the EIA or control groups had evidence of VCD at baseline or after undergoing MCT. Truncation of the inspiratory limb of the FVL after MCT was noted in five patients, which correlated with evidence of VCD in 60% of these patients. One EIA patient had truncation of the inspiratory FVL after MCT, and no changes were found in the control group. A comparison of spirometry between EIA patients and VCD patients with and without evidence of inspiratory vocal cord adduction during MCT showed no significant differences.

Conclusions: The findings suggest that MCT may cause an acute episode of vocal cord adduction and that positive results may not reflect underlying reactive airways disease. However, a flattening or truncation of the inspiratory FVL after the patient undergoes MCT is not diagnostic for the presence of inspiratory vocal cord adduction.

Key Words: bronchoprovocation • direct laryngoscopy • exercise-induced asthma • methacholine challenge testing • vocal cord dysfunction


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Vocal cord dysfunction (VCD) is a respiratory condition that is characterized by abnormal adduction of the vocal cords. Most commonly, VCD is manifested by a paradoxical inspiratory closure of the vocal cords, although it less frequently involves the expiratory phase. Symptoms include wheezing, chest tightness, shortness of breath, stridor, or exertional dyspnea.1 Patients with VCD are frequently misdiagnosed as having poorly controlled or exercise-induced asthma (EIA), and their response to standard asthma therapy is generally poor.2 These patients tend to present with recurrent symptoms on a frequent basis before the correct diagnosis is made. The diagnosis can be difficult since VCD mimics asthma but should be considered in those patients with inspiratory stridor or localized wheezing over the trachea. Direct visualization of the vocal cords via laryngoscopy remains the "gold standard" for the evaluation of patients with vocal cord abnormalities.3 4 Findings that are consistent with VCD on laryngoscopy include inspiratory closure of the vocal cords with posterior chinking (ie, a small opening at the posterior portion of the vocal cords), and some vocal cord closure may be seen during the expiratory phase.2 5 Flow-volume loop (FVL) testing during spirometry can reveal the characteristic flattening or truncation of the inspiratory limb that is consistent with variable extrathoracic obstruction, but this finding is generally absent unless patients are acutely symptomatic.5

A significant challenge in establishing the diagnosis of VCD is the similarity of its symptoms to those of asthma. There are numerous case reports of patients who have been treated incorrectly for asthma over long periods of time based on these symptoms. Bronchoprovocation testing is typically part of the evaluation of patients with normal baseline spirometry findings whose symptoms suggest asthma. Methacholine challenge testing (MCT) is a common procedure of choice for bronchoprovocation testing, with well-established guidelines having been set by the American Thoracic Society.6 That consensus statement recommends detecting inspiratory stridor during the examination and evaluating the inspiratory FVL for evidence of a plateau or flattening of the loop to diagnose VCD. The initial case series of five VCD patients in 1983 by Christopher et al2 demonstrated that all patients had normal spirometry values at baseline and that none had reactive airways after undergoing MCT or histamine challenge testing. Patients in other case series5 7 8 9 who had received diagnoses of either asthma or EIA had similar negative MCT findings. However, the results of other studies have suggested an overlap between VCD and asthma. The largest series of 95 VCD patients by Newman and Dubester10 established that 53% of VCD patients had coexistent asthma based on bronchoprovocation testing or peak flow variability. Thirty-five percent of patients in another case series11 of 20 patients also were found to have underlying obstructive airways disease.

In our prospective study evaluating patients who were in the US Army on active duty and had experienced exertional dyspnea, VCD patients demonstrated findings that suggested an overlap with reactive airways disease (RAD). MCT was positive for airway hyperresponsiveness in 60% of these patients. A review of their FVLs also demonstrated that 20% of patients had pre-MCT inspiratory limb flattening and that 60% had post-MCT inspiratory limb flattening. VCD patients likewise tended to have a smaller decrease in the FEV1/FVC ratio when compared to patients with a reactive MCT result.12 Other indirect evidence of VCD that was based on clinical findings of inspiratory stridor during MCT or acute changes in the inspiratory FVL has been noted in several case reports.13 14 15 In a case series by Selner et al,4 one patient developed acute laryngeal stridor during an initial MCT but subsequently had no further response to methacholine after psychology intervention. In another case series of four VCD patients with nocturnal awakening, two had reactive MCT results, with VCD suggested by the minimal change in the FEV1/FVC ratio from baseline.16

Currently, there are no studies that have specifically evaluated whether VCD can be induced by MCT. We investigated whether MCT can cause acute VCD based on direct visualization of the vocal cords. We then further compared post-MCT spirometry and FVL data in these patients with those of both EIA patients and healthy control subjects who were undergoing MCT to determine whether any changes were suggestive of the presence of VCD.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
The institutional review board approved this study protocol, and each patient signed an informed consent for participation in the study. Three groups of patients were enrolled. The first group consisted of asymptomatic control subjects who had been recruited from among active-duty Army personnel and were able to complete the Army 2-mile run in > 75% of the minimum standard. These subjects were required to have normal baseline spirometry and FVL values prior to enrollment. The second group consisted of patients with EIA, which was defined as symptomatic exertional dyspnea treated with as-needed inhaled ß-agonist agents, normal baseline spirometry values with normal FVL values, and prior positive results of MCT. Any EIA patient requiring chronic daily anti-inflammatory asthma medications was excluded. The third group of patients had documented VCD by direct laryngoscopy prior to entrance into the study. VCD patients were enrolled only if they had normal baseline spirometry values with no evidence of airways obstruction.

All patients and control subjects were required to refrain from ingesting caffeine and receiving any inhaled bronchodilators for at least 12 h prior to MCT. Each patient performed three FVC maneuvers at baseline, and the best effort was recorded. The patient then was administered increasing doses of methacholine mixed in a normal saline solution at the following concentrations: normal saline solution diluent only; 0.025 mg/mL; 0.25 mg/mL; 2.5 mg/mL; 10 mg/mL; and 25 mg/mL.17 Each patient was given the methacholine via five breaths (model 0700 dosimeter; Salter Labs; Arvin, CA) using an inspiratory time of 0.6 s. The patient waited 3 min and performed three FVC maneuvers. This was repeated for all concentrations of methacholine until the maximal concentration was reached or there was a 20% decline in the FEV1.

Each patient underwent direct laryngoscopy after baseline spirometry and again after meeting the criteria for the discontinuation of MCT or completing all dosages. Laryngoscopy was performed utilizing a flexible rhinolaryngoscope (model LP3; Olympus; Melville, NY). Each patient received 2% viscous lidocaine applied by cotton-tipped swabs in the nares for anesthesia. The posterior pharynx was intentionally not anesthetized in order to avoid any involvement of the vocal cords. The laryngoscope was directed to the posterior pharynx several centimeters above the glottis in order to prevent stimulation and adduction of the vocal cords. Observations were made of the vocal cords while the patient breathed quietly, spoke, and breathed rapidly for approximately 15 s each. Patients were specifically observed for evidence of vocal cord adduction during inspiration. Videotape records of vocal cord movement were made during the procedure, and an investigator blinded to the identity of each patient determined the presence or absence of vocal cord adduction during inspiration.

VCD patients were subdivided into the following two groups; VCD-positive (ie, evidence of vocal cord adduction post-MCT); and VCD-negative (ie, normal vocal cord movement post-MCT). Statistical comparisons of VCD patients, EIA patients, and control subjects were made using a one-way analysis of variance. A Mann-Whitney rank sum test was used when a normality test failed. Comparisons were made of the FEV1, FVC, and FEV1/FVC ratio for all four groups (pre-MCT, VCD-positive, VCD-negative, and EIA post-MCT). A p value of < 0.05 was considered to be significant. Statistical analysis was performed using commercially available software (SigmaStat, version 2.0; Jandel Scientific; San Rafael, CA).


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
A total of 34 patients were enrolled in the protocol. The VCD group (n = 10) consisted of two men and eight women with an average age (± SD) of 31.1 ± 15.6 years. The majority of patients had symptoms of exertional dyspnea as their presenting complaint prior to receiving a diagnosis of VCD. Two other patients had a history of poorly controlled asthma and gastroesophageal reflux disease. The demographics for each patient are shown in Table 1 . The EIA group (n = 12) consisted of four men and eight women with an average age of 34.3 ± 12.9 years. The control group (n = 12) consisted of six men and six women with an average age of 29.0 ± 8.0 years. All patients were able to complete MCT and laryngoscopy as previously described.


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  		Table 1.. Demographics of VCD Patients With Vocal Cord Findings and FVLs pre-MCT and post-MCT*

 
None of the EIA patients or control subjects had inspiratory vocal cord adduction pre-MCT or post-MCT. In the VCD group (Table 1) , two patients demonstrated inspiratory adduction at baseline prior to MCT, and both patients had identical findings post-MCT. These patients also had a history of poorly controlled asthma and gastroesophageal reflux with symptoms of VCD at rest. Two VCD patients had normal vocal cord motion pre-MCT but developed acute inspiratory adduction of the vocal cords post-MCT. The remaining six VCD patients had normal findings by direct laryngoscopy.

The pre-MCT and post-MCT Inspiratory FVLs were compared among the three groups. None of the subjects in the control group had flattening or truncation of the inspiratory limb of the FVL pre-MCT or post-MCT. One patient in the EIA group demonstrated flattening of the inspiratory FVL post-MCT. As shown in Table 1 , the VCD group had one patient with baseline inspiratory FVL flattening, but FVLs were unchanged post-MCT and no evidence of VCD was seen. Five VCD patients developed flattening of the FVL post-MCT. Two patients had acute VCD post-MCT. One patient showed evidence of VCD pre-MCT and post-MCT, and the remaining two showed no evidence of VCD during the study.

Table 2 shows the spirometry values for all groups. The control group had no reactive MCT, and there was minimal change in FEV1 and FVC from baseline. Patients in the EIA group all had reactive MCT results with an average decrease in FEV1 of 28.5 ± 4.7% from baseline. Overall, the VCD group met the criteria for reactive MCT results in 70% of patients. The VCD group was divided into the following two subgroups: patients with evidence of VCD during MCT (VCD-positive, four patients); and those with no evidence of VCD (VCD-negative, six patients). The VCD-negative group had 66% reactive MCT results with an average decrease in FEV1 of 20.7 ± 9.3% from baseline. The VCD-positive group had 75% reactive MCT results with an average decrease in FEV1 of 31.9 ± 24.8% from baseline. Statistical analysis of the comparison between EIA patients and patients in the two VCD subgroups showed no significant differences in FEV1, FVC, or FEV1/FVC ratio due to the small numbers in each VCD group and the large SDs.


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  		Table 2.. Spirometric Changes in Each Group of Patients Pre-MCT and Post-MCT*

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
VCD is a well-recognized cause of dyspnea, wheezing, and inspiratory stridor. Numerous case series and anecdotal reports describe how frequently VCD is incorrectly diagnosed and patients are treated for asthma. It becomes very important for the clinician to document the presence of airway hyperresponsiveness to help differentiate between VCD and asthma. However, the extent to which these two syndromes overlap has not been investigated previously. Our present study directly examined vocal cord movement and changes in spirometry and FVL in patients with documented VCD who were undergoing MCT. Our findings suggest that some patients with VCD will develop acute symptoms while undergoing MCT and will have false-positive results. Other patients may have evidence of VCD at baseline, and any changes in MCT may reflect either VCD or concomitant RAD. This evidence highlights the difficulty in differentiating between VCD and asthma based solely on bronchoprovocation testing.

Many experts believe that paradoxical VCD represents a conversion reaction that is associated with a variety of psychiatric conditions including depression,18 sexual abuse,19 severe emotional or physical stress such as that experienced during war,7 or may be triggered by exercise in highly competitive athletes.5 20 In the largest series of VCD patients, Newman and Dubester10 found that 73% of VCD patients had a major psychiatric disorder, 37% had a personality disorder, and 38% had a prior history of abuse. More recent studies have suggested that paradoxical VCD may be triggered by other causes. A retrospective case series from the National Jewish Medical and Research Center21 described 11 patients with irritant-induced VCD. These patients all developed VCD within 24 h of exposure to substances such as ammonia, flux flumes, cleaning chemicals, and smoke. It was speculated that these irritants might cause laryngeal inflammation that triggers VCD. Furthermore, these patients had fewer underlying psychosocial disorders when compared to patients with nonirritant VCD. In their series of 22 adolescents with VCD, Powell et al20 also noted that 95% of patients had posterior glottic changes with arytenoid and interarytenoid edema similar to gastroesophageal reflux disease. However, the association between reflux disease and VCD has not been established by any prospective studies.

Earlier studies demonstrated a relationship between glottic abnormalities and asthma. Histamine challenge testing has been shown to produce a narrowing of the glottic width during both inspiration and expiration.22 Since histamine (a smooth muscle irritant similar to methacholine) should not affect the laryngeal musculature, the effect was thought to be reflex narrowing due to a reduction in intrapulmonary airway caliber. This effect was further demonstrated to correlate with a decrease in FEV1 and to be more prominent in expiration.23 Other studies24 have demonstrated increased inspiratory resistance during panting maneuvers in some asthmatic patients (7 of 16 patients) due to inspiratory narrowing of the glottis and extrathoracic airway. Further evaluation by Collett et al25 showed a small change in inspiratory glottic dimension but substantial changes during expiration. It is thought that expiratory glottic narrowing may benefit asthma and allow hyperinflation by reducing inspiratory muscle activity that persists during expiration. However, there is no theorized benefit to inspiratory narrowing, and some authors26 theorize that there may be an overrecruitment of glottic constrictor muscles.

Methacholine both in this study and in other cases has been described as demonstrating some effect on the vocal cords. The only previous documented case by Selner et al4 in 1987 described a patient who underwent three MCT sessions. During the first methacholine challenge, stridor resulted at 5 mg/mL, but no change in peak flow was recorded. During the second challenge test, the patient reacted during the normal saline solution control test and developed acute VCD documented by laryngoscopy. A third challenge after psychological intervention resulted in no symptoms or VCD. The authors thought that there was primary and secondary gain by the patient to gain supportive maternal response and that the acute VCD symptoms were not due to the methacholine itself.

However, there has been ample indirect evidence to support the direct effect of MCT on VCD in some case reports and series. A recent case report by Parameswaran et al14 has suggested the presence of VCD induced by methacholine based on FVL, but direct laryngoscopy was not performed during the period of the patient’s acute symptoms. Another case report13 noted acute flattening of the inspiratory FVL at the maximum dose of methacholine, which returned to a normal level several minutes later. Our previous study12 noted that 60% of VCD patients had evidence of FVL changes post-MCT and that the FVLs were significantly increased compared to both patients with other causes of exertional dyspnea and normal control subjects.

FVLs had limited utility in this study. The two patients with evidence of VCD pre-MCT had normal FVLs. Conversely, the one patient with definite FVL truncation at baseline had normal vocal cord findings. Post-MCT, it was found that 50% of patients had definite FVL changes from baseline. However, this correlated with laryngoscopy findings in only two of these five patients. The 60% false-positive rate does not reliably predict the presence of VCD. A majority of patients with VCD (70%) met the criteria for abnormal lung volumes post-MCT (defined as a > 20% decline in FEV1), which is consistent with previously reported data.1 12 Four patients with positive MCT results had no evidence of VCD during the procedure and likely have a combination of VCD and reactive airways. The remaining three patients with positive MCT results also had evidence of VCD post-MCT. However, both groups are too small to compare the decrease in FEV1 and FEV1/FVC ratio to demonstrate any statistical difference as a means to differentiate these two disorders. Bucca et al27 suggested that the presence of extrathoracic airway hyperreactivity in such disorders as sinusitis, postnasal drip, and laryngitis might be diagnosed by a decrease in midexpiratory flows. While VCD was not specifically examined in their study, evaluating this measurement in future protocols may serve as a possible indicator of VCD during MCT.

Patients with VCD have a high incidence (> 70%) of reactive MCT. In some VCD patients, this is clearly due to a combination of both VCD and RAD. Other patients may have vocal cord adduction at baseline, and a reactive MCT result may reflect either process. A small percentage of patients with VCD will have acute inspiratory vocal cord adduction during MCT. Any changes in spirometry during MCT likely reflect acute VCD, and test results should not be interpreted as reflecting the presence of RAD. Methacholine may be the causative factor as a direct airway irritant, but this has not been definitely proven by this study. Other possibilities include the perceived emotional stress by the patient with VCD that is associated with MCT and that causes acute symptoms. The abnormal flattening or truncation of the inspiratory limb of the FVL after MCT, although not diagnostic, should alert the clinician to the possible presence of VCD. Those patients with reactive MCT results, changes in FVLs, and physical examination findings that are suggestive of upper airway obstruction should undergo further evaluation for VCD. While it has been established that VCD can be induced by MCT, further study in a larger population is necessary to define the incidence of reactive MCT among patients with VCD and to examine the significance of spirometry.


   Footnotes
 
Abbreviations: EIA = exercise-induced asthma; FVL = flow-volume loop; MCT = methacholine challenge testing; RAD = reactive airways disease; VCD = vocal cord dysfunction

The opinions or assertions contained herein are the private views of the authors and are not to be construed as reflecting the opinion of the Department of the Army or the Department of Defense.

MAJ Perkins was awarded the 2000 CHEST Foundation Young Investigator Award, at Chest 2000, San Francisco, CA, October 22 to 26, 2000.

Received for publication January 31, 2002. Accepted for publication June 26, 2002.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Newman, KB, Mason, UG, Schmaling, KB (1995) Clinical features of vocal cord dysfunction. Am J Respir Crit Care Med 152,1382-1386[Abstract]
  2. Christopher, KL, Wood, RP, Eckert, C, et al Vocal cord dysfunction presenting as asthma. N Engl J Med 1983;308,1566-1570[Abstract]
  3. Wood, RP, II, Milgrom, H Vocal cord dysfunction. J Allergy Clin Immunol 1996;98,481-485[CrossRef][ISI][Medline]
  4. Selner, JC, Staudenmayer, H, Koepke, JW, et al Vocal cord dysfunction: the importance of psychologic factors and provocation challenge testing. J Allergy Clin Immunol 1987;79,726-733[CrossRef][ISI][Medline]
  5. McFadden, ER, Zawadski, DK Vocal cord dysfunction masquerading as exercise-induced asthma a physiologic cause for "choking" during athletic activities. Am J Respir Crit Care Med 1996;153,942-947[Abstract]
  6. Crapo, RO, Casaburi, R, Coates, AL, et al Guidelines for methacholine and exercise challenge testing: 1999. Am J Respir Crit Care Med 2000;161,309-329[Free Full Text]
  7. Craig, T, Sitz, K, Squire, E Vocal cord dysfunction during wartime. Mil Med 1992;157,614-616[ISI][Medline]
  8. Kivity, S, Bibi, H, Schwarz, Y, et al Variable vocal cord dysfunction presenting as wheezing and exercise-induced asthma. J Asthma 1986;23,241-244[ISI][Medline]
  9. Thomas, PS, Geddes, DM, Barnes, PJ Pseudo-steroid resistant asthma. Thorax 1999;54,352-356[Abstract/Free Full Text]
  10. Newman, KB, Dubester, SN Vocal cord dysfunction: masquerader of asthma. Semin Respir Crit Care Med 1994;15,162-167
  11. O’Connell, MA, Sklarew, PR, Goodman, DL Spectrum of presentation of paradoxical vocal cord motion in ambulatory patients. Ann Allergy Asthma Immunol 1995;74,341-344[ISI][Medline]
  12. Morris, MJ, Deal, LE, Bean, DR, et al Vocal cord dysfunction in patients with exertional dyspnea. Chest 1999;116,1676-1682[Abstract/Free Full Text]
  13. Lakin, RC, Metzger, WJ, Haughey, BH Upper airway obstruction presenting as exercise-induced asthma. Chest 1984;86,499-501[Abstract/Free Full Text]
  14. Parameswaran, K, Cox, G, Kitching, A, et al Coronary and laryngeal spasm provoked by methacholine inhalation. J Allergy Clin Immunol 2001;107,392-393[Medline]
  15. Parker, JM, Mooney, LD, Berg, BW Exercise tidal loops in patients with vocal cord dysfunction. Chest 1998;114,2565
  16. Reisner, C, Nelson, HS Vocal cord dysfunction with nocturnal awakening. J Allergy Clin Immunol 1997;99,843-846[CrossRef][ISI][Medline]
  17. Eliasson, AH, Phillips, YY, Rajagopal, KR, et al Sensitivity and specificity of bronchial provocation testing. Chest 1992;102,347-355[Abstract/Free Full Text]
  18. Brown, TM, Merritt, WD, Evans, DL Psychogenic vocal cord dysfunction masquerading as asthma. J Nerv Ment Dis 1988;176,308-310[ISI][Medline]
  19. Tajchman, UW, Gitterman, B Vocal cord dysfunction associated with sexual abuse. Clin Pediatr (Phila) 1996;35,105-108
  20. Powell, DM, Karanfilov, BI, Beechler, KB, et al Paradoxical vocal cord dysfunction in juveniles. Arch Otolaryngol Head Neck Surg 2000;126,29-34[Abstract/Free Full Text]
  21. Perkner, JJ, Fennelly, KP, Balkissoon, R, et al Irritant-associated vocal cord dysfunction. J Occup Environ Med 1998;40,136-143[CrossRef][ISI][Medline]
  22. Higenbottam, T Narrowing of glottis in humans associated with experimentally induced bronchospasm. J Appl Physiol 1980;49,403-407[Abstract/Free Full Text]
  23. Higenbottam, T, Payne, J Glottis narrowing in lung disease. Am Rev Respir Dis 1982;125,746-750[ISI][Medline]
  24. Lisboa, C, Jardim, J, Angus, E, et al Is extrathoracic airway obstruction important in asthma? Am Rev Respir Dis 1980;122,115-121[Medline]
  25. Collett, PW, Brancatisano, AP, Engel, LA Changes in the glottic aperture during bronchial asthma. Am Rev Respir Dis 1983;128,719-723[ISI][Medline]
  26. Elshami, AA, Tino, G Coexistent asthma and functional upper airway obstruction: case reports and review of the literature. Chest 1996;110,1358-1361[Abstract/Free Full Text]
  27. Bucca, C, Rolla, G, Brussino, L, et al Are asthma-like symptoms due to bronchial or extrathoracic airway dysfunction? Lancet 1995;346,791-795[CrossRef][ISI][Medline]



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