Table 2.
Review of the studies that comply with international and Australian guidelines for the performance of sweat testing.
| Study | Sample size (n) | Selection criteria* | Age range (years) | Sweat test method | Sweat electrolyte concentrations (mmol/L) | Study limitations† | |
|---|---|---|---|---|---|---|---|
| Chloride (Cl−) | Sodium (Na+) | ||||||
| Hopkins Study (Gibson and Cooke, 1959)9 | Total: n = 89 |
Stimulation: pilocarpine iontophoresis
Collection: in two different medium: 15–90 minutes on gauze squares (3x3inch) and 30 minutes on filter-paper disks (2.5cm) Analysis: chloride–polarographic method |
- Not a healthy control group, thus possible that these subjects had a condition that affects sweat electrolytes or had a mild CF phenotype.
- No mention of subjects’ age. - Relatives have a higher risk of being a carrier. - This study was conducted prior to the discovery of the CFTR gene. |
||||
| 25 | 1.CF: history of excessive appetite, steatorrhoea and recurrent pulmonary disease | Not stated |
3x 3 inch gauze squares: n=14: Mean: 110.1 SD: NR Range: 84–136 2.5cm filter-paper disks n=11: Mean: 94.8 SD: NR Range: 80–122 |
Mean: NR
SD: NR Range: NR |
|||
| 47 | 2. Non-CF: 3 apparently healthy, 20 had asthma, 8 recurrent bronchitis, 3 hepatitis, 2 congenital heart disease, 1 each had non-tropical sprue, osteomyelitis, pyelonephritis, bronchiectasis, hypertension | Not stated |
3x 3 inch gauze squares: n=8: Mean: 45.4 SD: NR Range: 11–60 2.5 cm filter-paper disks n=39: Mean: 21.1 SD: NR Range: 7–49 |
Mean: NR
SD: NR Range: NR |
|||
| 17 | 3. Asymptomatic relatives of CF | Not stated |
3x 3 inch gauze squares: n=12: Mean: 33.9 SD: NR Range: 12–57 2.5cm filter-paper disks n=5: Mean: 32.5 SD: NR Range 16–47 |
Mean: NR
SD: NR Range: NR |
|||
| Washington Study (Andrews et al, 1962)28 | Total: n = 66 |
Stimulation: pilocarpine iontophoresis
Collection: 30 minutes on filter paper Analysis: chloride–coulometric |
- Small number of subjects in each group.
- Siblings have 2/3 risk of being a carrier. - This study was conducted prior to the discovery of the CFTR gene. - It is also possible that the control group had a condition that affects sweat electrolytes or had a mild CF phenotype. |
||||
| 6 | 1. CF | 1–4.5 | Mean: 110
SD: NR Range: 84-154 |
Mean: NR
SD: NR Range: NR |
|||
| 6 | 2. Asymptomatic siblings of patients with CF | 0.3-6 | Mean: 34.8
SD: NR Range: 19-53 |
||||
| 27 | 3a. non-CF symptomatic: allergic children with rhinitis, eczema, asthma without emphysema, nasal eosinophilia | 0.7-10 | Mean: 19.7
SD: NR Range: 9-35 |
||||
| 11 | 3b. non-CF symptomatic: children with asthma, evidence of emphysema | 1-10 | Mean: 26.5
SD: NR Range: 7-60 |
||||
| 16 | 4. non-CF asymptomatic: no history of allergic or pulmonary disease | 0.4–9 | Mean: 16.7
SD: NR Range: 5–33 |
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| Colorado Study (Gharib et al, 1965)32 | Total: n = 255 |
Stimulation: pilocarpine iontophoresis
Collection: 30 minutes on filter paper Analysis: sodium – flame photometry chloride – titration with mercuric nitrate |
- Not a ‘healthy’ control group. Group 2b includes patients with infections, siblings of CF patients (higher risk of being a carrier) and various other medical conditions. It is possible that some of these subjects had a condition that affects sweat electrolytes or had a mild CF phenotype.- The study was conducted prior to the discovery of the CFTR gene.- Subjects’ age not mentioned in Group 2b. | ||||
| 100 | 1. CF: M:F – 46:54 | <5–15 | Mean: 109
SD: ± 17 Range: 60–186 |
Mean: NR
SD: NR Range: NR |
|||
| 100 | 2a. non-CF symptomatic: patients with allergic bronchial asthma (M:F – 65:35) | <5–15 | Mean: 12.3
SD: ± 7 Range: 2.7–39 |
||||
| 55 | 2b. non-CF symptomatic: patients with frequent respiratory tract infections, chronic diarrhoea, family history of CF, failure to thrive, sepsis, rectal prolapse (M:F – 30:25) | Not stated | Mean: 14.7
SD: ± 6 Range: 4–33 |
||||
| Minneapolis Study (Warwick and Hansen, 1978)30 | Total: n = 100 |
Stimulation: pilocarpine iontophoresis by two methods
A. Orion ‘ionto-block’ method B. ‘Gibson and Cooke’ method Collection: 5 minutes on parafilm (10x10cm) Analysis: chloride–potentiometer with chloride selective electrode |
- Orion electrode has been proven to give inaccurate results due to insufficient collection time and should not be used.38 - Recruitment criteria not defined. - It is possible that the asymptomatic subjects had a condition that affects sweat electrolytes or had a CF- related condition. - This study was conducted prior to the discovery of the CFTR gene. - No mention of subjects’ age. |
||||
| 50 | 1. CF | Not stated |
Orion method Mean: 100.2 SD: ± 25.4 Range: NR Gibson-Cooke Mean: 103.7 SD: ± 21.6 Range: NR |
Mean: NR
SD: NR Range: NR |
|||
| 50 | 2. non-CF asymptomatic | Not stated |
Orion method Mean: 11.4 SD: ± 6.9 Range: NR Gibson-Cooke Mean: 9.3 SD: ± 5.8 Range: NR |
||||
| Boston Study (Shwachman et al, 1981)26 | Total: n = 504 |
Stimulation: pilocarpine iontophoresis
Collection: 30 minutes on gauze pad Analysis: chloride–titration with mercuric nitrate |
- Not a ‘healthy’ control group. Controls were referred for clinical reasons and were later found not to have CF. It is possible that some subjects had a condition that affects sweat electrolytes or had a mild CF phenotype.
- This study was conducted prior to the discovery of the CFTR gene. |
||||
| 252 | 1. CF: n = 252 | Not stated | Mean: 115.3
SD: ± 12.1 Range: 78.6-148.2 |
Mean: 111.2
SD: ± 12.0 Range: 75.4-144.6 |
|||
| 252 | 2. non-CF asymptomatic: children referred for clinical reasons but were excluded of CF | Not stated | Mean: 28.0
SD: ± 6.0 Range: 7.7-43.4 |
Mean: 28.2
SD: ± 6.1 Range: 15.9-45.9 |
|||
| Ohio Study (Davis et al, 1982)29 | Total: n = 200 |
Stimulation: pilocarpine iontophoresis
Collection: 30 minutes on filter paper Analysis: chloride–coulombmetric titration |
- Not a ‘healthy’ control group.
- Recruitment criteria not defined. - This study was conducted prior to the discovery of the CFTR gene. - No separate data for 21 healthy controls. - Exact age of the subjects was not mentioned. |
||||
| 13 | 1. CF: hospitalised CF patients with chronic pulmonary disease | 22.5 ± 2 (SD) | Mean: 100.1
SD: ± 7.2 Range: NR |
Mean: NR
SD: NR Range: NR |
|||
| 21 | 2a. non-CF asymptomatic: healthy volunteers | 53.5 ± 14.7 (SD) | Mean: 25.7
SD: ± 15.5 Range: NR |
||||
| 166 | 2b. non-CF symptomatic: patients with various pulmonary disorders such as asthma, allergies, chronic obstructive pulmonary disease | ||||||
| Birmingham Study (Hall et al, 1990)27 | Total: n = 60 |
Stimulation: pilocarpine iontophoresis
Collection: on filter paper and the time was reduced to 20 minutes (or less if the paper was visibly wet) Analysis: sodium–flame photometry chloride–potentiometric |
- It is possible that the asymptomatic subjects had a condition that affects sweat electrolytes or had a mild CF phenotype.
- No CFTR gene mutation analysis to exclude carriers or mild CF. - Small number of subjects. |
||||
| 20 | 1.CF: diagnosed in childhood by clinical features and positive sweat test (M:F–12:8) | 18-31 | Mean: 106
SD: NR Range: 81-122 |
Mean: 108
SD: NR Range: 84-137 |
|||
| 20 | 2. non-CF symptomatic: patients undergoing investigation for chest disease other than CF (M:F–13:7) | 19-40 | Mean: 33
SD: NR Range 13-52 |
Mean: 52
SD: NR Range 29-77 |
|||
| 20 | 3. non-CF asymptomatic: normal adults with no history of chest or digestive disease (M:F–7:13) | 18-39 | Mean: 31
SD: NR Range: 14-48 |
Mean: 50
SD: NR Range 29-72 |
|||
| Edinburgh Study (Kirk et al, 1992)24 | Total: n = 233 |
Stimulation: pilocarpine iontophoresis
Collection: by two methods:- 30 minutes on filter paper - Wescor Macroduct Analysis: sodium–flame photometry chloride–colorimetric |
- Combined the asymptomatic and symptomatic controls into non-CF group.
- Recruitment criteria for Group 2b not defined. - Small number of asymptomatic subjects. - Group 2a had 97 subjects referred for clinical reasons, therefore, it is possible that some subjects had a condition that affects sweat electrolytes, or had a mild CF phenotype. - CFTR gene mutation analysis was performed on the CF group, but not on the non-CF group to exclude carriers or mild CF. |
||||
| 121 | 1. CF: patients attending the CF clinics (M:F–66:55) | 0-40 | n = 112:
Mean: 100 SD: NR Range 70-132 n=9: Cl− = 51-69 SD: NR Range: NR |
n = 112:
Mean: 103 SD: NR Range: 70-132 (The nine patients with equivocal Cl− results had Na+ results of 70- 102 mmol/L) |
|||
| 97 | 2a. non-CF symptomatic: referred for the sweat test for clinical reasons | 0-40 | n = 112:
Mean: 22.5 SD: NR Range: 3-53 (Of 112 non-CF subjects, 2 had sweat chloride > 50 mmol/L) |
Mean: 40.3
SD: NR Range: 5-81 |
|||
| 15 | 2b. non-CF asymptomatic | ||||||
| Monash Medical Centre (Melbourne) Study (Doery and Huang, 1993) (Abstract)36 | Total: n = 250 |
Stimulation: pilocarpine iontophoresis
Collection: 45–60 minutes on filter paper Analysis: sodium–flame photometry chloride – colorimetry |
- Small number of CF patients recruited.
- Not a healthy control group. The non-CF group included patients referred for sweat tests. It is possible that these subjects had a condition that affects sweat electrolytes or had a mild CF phenotype. - Small number of non-CF patients in age group 10+ years. - This study was conducted after the discovery of the CFTR gene, but no mutation analysis was performed to exclude carriers. |
||||
| 9 | 1. CF | 0–4 | Mean: 97.8
SD: ± 17 Range: 73–124 |
Mean: 78
SD: ± 16 Range: 52–104 |
|||
| 125 | 2a-d. non-CF symptomatic: subjects with chest symptoms – cough, wheeze and recurrent upper respiratory tract infection | 0–1 | Mean: 13.5
SD: ± 5.6 Range: 3–38 |
Mean: 14.6
SD: ± 5.7 Range: 4–30 |
|||
| 80 | 1–5 | Mean: 16.1
SD: ± 6.0 Range: 7–39 |
Mean: 17.6
SD: ± 7.3 Range: 3–43 |
||||
| 25 | 5–10 | Mean: 17
SD: ± 7.6 Range: 7–36 |
Mean: 20.4
SD: ± 7.5 Range: 8–40 |
||||
| 11 | 10+ | Mean: 23.7
SD: ± 10.5 Range: 10–41 |
Mean: 32.3
SD: ± 13.2 Range: 10–53 |
||||
| Wisconsin Study (Farrell and Koscik, 1996)31 | Total: n = 707 |
Stimulation: pilocarpine iontophoresis
Collection: 30 minutes on filter paper Analysis: chloride –digital chloridometer |
- Exact age not mentioned.
- The sweat chloride concentrations for infants and carriers were non- parametric, yet the concentrations are reported as mean and SD. - Not a healthy control group, as the non-CF group included infants with a positive NBS test result, and infants referred for sweat tests due to clinical reasons and thus to rule out CF e.g. recurrent respiratory symptoms. - It is possible that some infants may be carriers for other mutations, although the chances are very low. |
||||
| 61 | 1a. CF: ΔF508/ΔF508 homozygote infants | 10.5 ± 9.9 (weeks) | Mean: 100.0
SD: ± 9.2 Range: NR |
Mean: NR
SD: NR Range: NR |
|||
| 47 | 1b. CF: ΔF508 compound heterozygote infants | 9.3 ± 9.3 (weeks) | Mean: 97.6
SD: ± 15.3 Range: NR |
||||
| 7 | 1c. CF: infants with non-ΔF508 mutations | 16.5 ± 17.3 (weeks) | Mean: 99.6
SD: ± 14.1 Range: NR |
||||
| 128 | 2. heterozygote carriers | 8.8 ± 5 (weeks) | Mean: 14.9
SD: ± 8.4 Range: NR |
||||
| 184 | 3a. non-CF symptomatic: normal (no mutation) | 9.3 ± 5.3 (weeks) | Mean: 10.6
SD: ± 5.2 Range: NR |
||||
| 280 | 3b. non-CF symptomatic: normal (no gene mutation analysis performed) | 21.2 ± (13.1) | Mean: 11.6
SD: ± 5.3 Range: NR |
||||
List of abbreviations: CFTR = cystic fibrosis transmembrane conductance regulator; ΔF508 = deletion of phenylalanine at position 508; M:F = Male:Female; n = number of subjects; NBS = Newborn screening; NR = not reported; RCH = The Royal Children’s Hospital; SD = standard deviation.
*
CF = Subjects that were diagnosed with CF based on clinical features and/or sweat test and/or mutation analysis.
non-CF asym
selection criteria for their ‘control’ group are assumed to have no known disease are also included in this group.
non-CF symptomatic: Subjects that were not diagnosed with CF but had other known disease.
†
Study limitations: This section includes the critical interpretation of the study by the reviewers.