Online supplement
Table a Immunological abnormalities
Abnormality
Low IgG, IgM, IgG2, haemophilus antibody response
IgG and IgG1 low
IgG, IgG1 and IgG2 low
IgG, IgA and IgG2 low
IgG, IgG1, IgG2, haemophilus and pneumococcus antibody responses all low
IgG, IgG2 and IgG3 repeatedly low
IgG2 and haemophilus antibody responses low
Haemophilus and pneumococcus antibody responses
Low IgA, IgG, IgG2, IgG3
Repeatedly low IgG and IgG2
Ig,Immunoglobulin n Atopic status
1 Atopic
1 Atopic
1 Atopic
1 Atopic
1 Atopic
1 Non atopic
1 Non atopic
1 Non atopic
1 Non atopic
1 Non atopic
1
Table b High Resolution CT Results
CT change
Normal
Bronchial wall thickening
Small airways disease/air trapping
Bronchiectasis
Bronchial wall thickening & small airways disease
Other
Atopic
(n=39)
12/39 (31)
11/39 (28)
9/39 (23)
1/39 (3)
4/39 (10)
Non atopic
(n=8)
1/8 (13)
0/8 (0)
2/8(25)
2/8(25)
2/8(25)
Double aortic arch (n=1)
RML Collapse +BWT
(n=1)
1/8 (13)
- narrow trachea
Data represented as number positive/number who had test (%). BWT, bronchial wall thickening;
RML, right middle lobe
2
Table c Bacterial growth from bronchoalveolar lavage
Bacterial growth Number positive
(n=19)
Staphylococcus aureus
Streptoccous pneumoniae
Haemophilus influenzae ,
Pseudomonas influenzae and streptococcus pneumoniae
H influenzae, Streptococcus pneumoniae and
Branhamella Catarrhalis
Haemophilus influenzae and streptococcus pneumoniae
8/19
5/19
2/19
1/19
1/19
2/19
*5 patients did not have bronchoalveolar cytology performed
Concurrent neutrophilia in
BAL
(n=15)*
3/5
3/4
1/2
1/1
1/1
1/2
3
Table d Significant alternative diagnoses
Atopic status
Condition
Atopic Sinusitis
Atopic Bronchiectasis
Atopic Vascular ring
Atopic
Job’s syndrome
Non Bronchiectasis – Primary atopic ciliary dyskinesia
Intervention Dose inhaled corticosteroid
(1yr follow up)
Endoscopic sinus surgery Stopped
Physiotherapy, azithromycin Same dose
Corrective surgery Reduced by 75%
Regular septrin Same
Physiotherapy, azithromycin Reduced by 80%
4
Table e Significant co-morbidities diagnosed during protocol
Condition Intervention
Atopic
Non atopic
Non atopic
Vocal cord dysfunction
& large tonsils
Severe gastro-oesphageal reflux
Severe gastro-oesphageal reflux & immune abnormalities
Psychological interventions & breathing techniques, tonsillectomy
Anti reflux treatement
Optimised anti reflux treatment
Dose inhaled corticosteroid
(1yr follow up)
Weaned by 50% at 2 yr follow up
Stopped
Reduced by 50%
5
Table f Comparison of children with symptom response vs non response
Atopy
Male
Smokers at home
History intubation
Pets present at home
Age (mean, SD, range)
Median IgE (range)
Mean % predicted FEV
1
(SD)
Baseline
Post steroid trial
FEV
1
abnormal
Baseline
Post steroid trial
Median % BDR (range)
Baseline
Post steroid trial
BDR present at
Baseline (number)
Post steroid trial
FeNO abnormal
Baseline
Post steroid trial
BAL eosinophilia
BAL neutrophilia
EB eosinophilia
EB neutrophilia
EB reticular basement membrane thickening
Steroid trial group
(n=81)
74/81 (91)
48/81 (51)
31/79 (39)
29/81 (36)
10/81 (12)
11.8 (2.6) (6-19)
654 (8-11355)
65.4 (19)
77.25 (18.3)
57/78 (73)
40/75 (53)
19.5 (0-130)
10 (0-82)
48/68 (71)
28/64 (44)
33/65 (51)
17/68 (25)
22/53 (42)
23/53 (43)
28/54 (52)
27/54 (50)
32/41 (78)
*Symptom response
(n=37)
33/37 (89)
25/37 (68)
10/36 (28)
5/36 (14)
14/37 (38)
11.2 (2.4)(7-16)
819 (31-11355)
64.7 (19.2)
80.5 (17.4)
25/35 (71)
16/35 (46)
19 (0-130)
8 (0-65)
24/31 (77)
10/29 (34)
16/31 (52)
5/31 (16)
9/25 (36)
14/25 (56)
12/26 (46)
17/26 (65)
16/21 (76)
Symptom non response
(n=38)
36/38 (95)
2/38 (5)
19/37 (51)
4/38 (11)
11/38 (29)
11.9 (2.7)(6-17)
623 (17-5014)
65.4 (19.2)
73.2 (19.1)
29/38 (76)
24/37 (65)
15 (0-79)
12 (0-82)
21/34 (62)
18/33 (55)
15/31 (48)
10/34 (29)
10/24 (42)
8/24 (33)
15/24 (63)
9/24 (38)
15/19 (79) p value
NS
NS
0.04
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
0.05
NS
Data represented as number positive/number who had test (%). BAL: bronchoalveolar lavage; BDR: % bronchodilator reversibility; EB: endobronchial biopsy; FeNO: fractional exhaled nitric oxide; FEV
1
: Forced expiratory volume in 1 second expressed as % predicted for height; IgE: immunoglobulin E; SD: standard deviation. *Defined as symptomatic improvement or resolution at the end of trial, data available in 75 patients only.
6
Table g Comparison of children with FEV
1
response vs non response
Atopy
Male
Smokers at home
Pet present at home
History intubation
Mean age (years, SD, range)
Median IgE (IU/ml, range)
Mean FEV
1
(SD)
Baseline
Post steroid trial
Baseline FEV
1
normal
Median % BDR (range)
Baseline
Post steroid trial
BDR present at
Baseline
Post steroid trial
FeNO abnormal
Baseline
Post steroid trial
Symptoms better
BAL eosinophilia
BAL neutrophilia
EB eosinophilia
EB neutrophilia
EB reticular basement membrane thickening
Steroid trial group
(n=81)
74/81 (91)
48/81 (59)
31/79 (39)
29/81 (36)
10/81 (12)
11.8 (2.6) (6-19)
654 (8-11355)
65.4 (19)
77.25 (18.3)
21/78 (27)
19.5 (0-130)
10 (0-82)
47/67 (70)
28/64 (44)
32/65 (49)
17/68 (25)
37/75 (49)
22/53 (42)
23/53 (43)
28/54 (52)
27/54 (50)
32/41 (78)
*FEV
1
response
(n=35)
32/35 (91)
19/35 (54)
16/35 (46)
14/35 (40)
4/35 (11)
11.3 (2.7)(6-17)
686.5 (26-11355)
74.2 (17.8)
92.9 (9.3)
14/34 (41)
19.9 (0-57)
5 (0-16)
23/30 (77)
5/27 (19)
13/26 (50)
8/28 (29)
19/32 (59)
11/20 (55)
9/20 (45)
14/24 (58)
14/25 (56)
13/17 (76)
FEV
1
non response
(n=40)
36/40 (90)
25/40 (63)
14/38 (37)
12/30 (40)
5/39 (13)
12 (2.2)(6-16)
700 (17-5680)
55 (16)
63.5(12)
4/39 (10)
24 (0-130)
13.5 (0-82)
24/37 (65)
23/37 (62)
17/35 (49)
8/37 (22)
16/40 (40)
9/28 (32)
13/28 (46)
14/27 (52)
14/27 (52)
17/21 (81) p value
NS
NS
NS
NS
NS
NS
NS
0.000
0.000
0.002
NS
0.000
NS
0.001
NS
NS
NS
NS
NS
NS
NS
NS
Data represented as number positive/number who had test (%). BAL: bronchoalveolar lavage; BDR: % bronchodilator reversibility; EB: endobronchial biopsy; FeNO: fractional exhaled nitric oxide; FEV
1
: Forced expiratory volume in 1 second expressed as % predicted for height; IgE: immunoglobulin E; SD: standard deviation. *Defined as FEV
1
≥80% predicted at the end of trial, 75 patients had pre/post data.
7
Table h Comparison of children with BDR response vs non response
Atopy
Male
Smokers at home
History intubation
Pet present
Mean age (SD, range)
Median IgE (range)
Mean % predicted FEV
1
(SD)
Baseline
Post steroid trial
FEV
1
abnormal
Baseline
Post steroid trial
Median % baseline BDR (range)
BDR present at baseline
FeNO abnormal
Baseline
Post steroid trial
Symptoms better
BAL eosinophilia
BAL neutrophilia
EB eosinophilia
EB neutrophilia
EB reticular basement membrane thickening
Steroid trial group
(n=81)
74/81 (91)
48/81 (59)
31/79 (39)
29/81 (36)
10/81 (12)
11.8 (2.6) (6-19)
654 (8-11355)
65.4 (19)
77.25 (18.3)
57/78 (73)
40/75 (53)
19.5 (0-130)
48/68 (71)
32/65 (49)
17/68 (25)
37/75 (49)
22/53 (42)
23/53 (43)
28/54 (52)
27/54 (50)
32/41 (78)
*BDR response
(n=36)
34/36 (94)
21/36 (58)
17/35 (35)
7/35 (20)
12/36 (33)
11.5 (2.5)(6-17)
690.5(26-5518)
66.4 (17.9)
84 (14.5)
28/35 (80)
14/36 (39)
22.9 (0-130)
25/35 (71)
14/29 (48)
5/30 (17)
19/34 (56)
11/24 (46)
12/24 (50)
13/26 (50)
15/26 (58)
15/19 (79)
BDR non response
(n=28)
25/28 (89)
18/28 (64)
10/27 (37)
2/28 (7)
10/28 (36)
11.5(2.7)(6-16)
852 (17-11355)
62.8 (20.4)
65.3 (16.7)
20/27 (74)
23/28 (82)
18 (0-79)
17/25 (68)
13/24 (54)
9/26 (35)
10/28 (36)
7/18 (39)
7/18 (39)
10/18 (50)
10/18 (56)
12/14 (86) p value
NS
NS
NS
NS
NS
NS
NS
NS
0.000
NS
0.001
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
Data represented as number positive/number who had test (%). BAL: bronchoalveolar lavage; BDR: % bronchodilator reversibility; EB: endobronchial biopsy; FeNO: fractional exhaled nitric oxide; FEV
1
: Forced expiratory volume in 1 second expressed as % predicted for height; IgE: immunoglobulin E; SD: standard deviation. *Defined as negative BDR test at end of trial, 64 patients had BDR pre/post corticosteroid trial.
8
Table I Comparison of children with FeNO response vs non response
Atopy
Male
Smokers at home
History intubation
Pet present
Age (mean, SD, range)
Median IgE (range)
Mean % predicted FEV
1
(SD)
Baseline
Post steroid trial
FEV
1
abnormal
Baseline
Post steroid trial
Median BDR (%)
Baseline
Post steroid trial
BDR present at
Baseline (number)
Post steroid trial
Symptoms better
FeNO normal at baseline
BAL eosinophilia
BAL neutrophilia
EB eosinophilia
EB neutrophilia
EB reticular basement membrane thickening
Steroid trial group
(n=81)
74/81 (91)
48/81 (51)
31/79 (39)
29/81 (36)
10/81 (12)
11.8 (2.6) (6-19)
654 (8-11355)
65.4 (19)
77.25 (18.3)
57/78 (73)
40/75 (53)
19.5 (0-130)
10 (0-82)
48/68 (71)
28/64 (44)
37/75 (49)
33/65 (51)
22/53 (42)
23/53 (43)
28/54 (52)
27/54 (50)
32/41 (78)
FeNO response*
(n=53)
47/53 (89)
32/53 (60)
22/51 (43)
6/52 (12)
19/53 (36)
11.7 (2.6)(6-17)
623 (17-5680)
64.5 (18.9)
76.3 (19.4)
39/52 (75)
30/51 (59)
18.3 (0-130)
10 (0-82)
29/45 (64)
18/44 (41)
26/52 (50)
28/47 (60)
12/32 (38)
13/32 (41)
17/35 (49)
18/35 (51)
21/27 (78)
FeNO non response
(n=17)
17/17 (100)
11/17 (65)
5/17 (29)
1/17 (6)
5/12 (41)
13(2.3) (9-19)
1044 (8-11355)
69.4 (18.2)
77.8 (16)
13/17 (76)
8/16 (50)
24 (5.7-79)
13.5 (0-35)
12/15 (80)
9/14 (64)
5/15 (33)
2/14 (14)
8/13 (62)
5/13 (38)
10/13 (77)
8/13 (62)
10/12 (83)
p value
NS
NS
NS
NS
NS
0.003
NS
NS
0.07
NS
NS
NS
NS
NS
NS
0.086
NS
NS
NS
NS
NS
NS
Data represented as number positive/number who had test (%). BAL: bronchoalveolar lavage; BDR: % bronchodilator reversibility; EB: endobronchial biopsy; FeNO: fractional exhaled nitric oxide; FEV
1
: Forced expiratory volume in 1 second expressed as % predicted for height; IgE: immunoglobulin E; SD: standard deviation. *Defined as normal FENO at the end of trial, 70 patients had FeNO performed pre/post corticosteroid trial.
9
Table j Persistent airflow limitation
Atopy
Male
Smokers at home
History intubation
Pets present
Age (mean, SD, range)
Median IgE (range)
Baseline mean % predicted FEV
1
Baseline FEV
1
abnormal
Baseline median % BDR
Baseline number with BDR present
FeNO abnormal
Baseline
Post steroid trial
Symptoms better
BAL eosinophilia
BAL neutrophilia
EB eosinophilia
EB neutrophilia
EB reticular basement membrane thickening
Steroid trial group
(n=81)
74/81 (91)
48/81 (59)
31/79 (39)
29/81 (36)
10/81 (12)
11.8 (2.6) (6-19)
654 (8-11355)
65.4 (19)
57/78 (73)
19.5 (0-130)
48/68 (71)
32/65 (51)
17/70 (24)
37/75 (49)
22/53 (42)
23/53 (43)
28/54 (52)
27/54 (50)
32/41 (78)
No persistent airflow limitation
(n=59)
54/57 (95)
36/59 (61)
22/58 (38)
7/58 (121)
26/59 (44)
(2.4) (6-17)
(26-11355)
(17.8)
35/56 (63)
18.6 (0-130)
36/50 (72)
23/47 (49)
12/49 (24)
30/53 (57)
15/36 (42)
15/36 (41)
20/40 (50)
18/40 (20)
24/31 (77)
*Persistent airflow limitation
(n=17)
15/17 (88)
9/17 (53)
8/16 (50)
3/17 (18)
2/17 (12)
13 (1.9) (9-16)
640.5 (17-5518)
50 (13.4)
17/17 (100)
27.5 (1.6-79)
10/15 (75)
7/15 (47)
4/15 (27)
6/17 (35)
6/13 (46)
7/13 (54)
7/11 (64)
7/11 (64)
6/8 (75) p value
NS
NS
NS
NS
0.02
NS
NS
<0.001
0.039
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
Data represented as number positive/number who had test (%). BAL: bronchoalveolar lavage; BDR: % bronchodilator reversibility; EB: endobronchial biopsy; FeNO: fractional exhaled nitric oxide; FEV
1
: Forced expiratory volume in 1 second expressed as % predicted for height; IgE: immunoglobulin E; SD: standard deviation *Defined as FEV
1
<80% predicted post bronchodilator & post corticosteroid trial
10
Analysis of children on systemic corticosteroids at baseline
Table k Comparison of corticosteroid response
Steroid response
Complete
Not on systemic corticosteroids
(n=51)
8/51 (16)
Partial
Non
36/51 (71)
7/51 (14)
On systemic corticosteroids
(n=30)
1/30 (3)
29/30 (97)
0/30 (0)
Table l Each parameter analysis
Parameter
Symptomatic response
Not on systemic steroids
26/49 (53%)
On systemic steroids
11/27 (41%)
FEV
1
(% pred)
BDR (%) pre
70
(32-102)
20 post
79
(49-125)
10 change
11
(-24-88)
-12 pre post
61 77
(27-109)
19
(37-106)
9.4 change
10
(-41-58)
-3
FeNO z score
FeNO
50
(ppb)
(0-130)
0.03
(-3.5-4)
(0-82)
-1.05
(-4.2-2)
(-126-19)
-1.16
(-4.3-1.1)
(0-55)
-1.33
(-3-2.6)
(0-42)
-1.38
(-4.9-1.4)
(-44-42)
-0.7
(-5.3-3.8)
25
(6-257)
13
(2-79)
-13.6
(-234-33)
12.7
(7-113)
12
(2-58)
-8
(-56-9)
Numerical values show the median and range. The symptomatic response data shows the number over the number tested and percentage in brackets .
BDR: bronchodilator reversibility; FeNO: Fractional exhaled nitric oxide; FeNO
50
: Fractional exhaled nitric oxide at flow rate 50ml/second; FEV
1: forced expiratory volume in 1 second p
NS (0.3)
NS (0.5)
NS(0.5)
NS (0.4)
NS (0.3)
11
Comparison of type of systemic steroid used in corticosteroid trial
Table m Comparison of corticosteroid response and route of steroid administration used
Steroid response Oral prednisolone
(n=65)
IM triamcinolone
(n=16)
Complete 8/65 (12) 1/16 (6)
Partial
Non
Parameter
Symptomatic response
50/65 (77)
7/65 (11)
15/16 (94)
0/16 (0)
Table n Comparison of response in each parameter and route of steroid administration used
Prednisolone
26/61 (43)
IM Triamcinolone
11/15
*
(73)
FEV
1
BDR
(% pred)
(%) pre
57
(27-109)
18
(0-130) post
79
(37-125)
11
(0-82)
Change
10
(-41-81)
-10
(-126-42) pre Post
61 77
(36-102)
24
(2-53)
(53-104)
10
(0-35) change
16
(-17-54)
-14
(-48-13)
FeNO z score -0.4
(-3.5-2.9)
-1.6
(-4.9-2)
1.1
(-5.3-1.8)
1.1
(-2.7-4)
-0.1
(-3.1-1.5)
-0.9
(-4.1-0.8)
FeNO
50
(ppb) 19 11 -7 48 24 -22
(6-113) (2-79) (-89-33) (21-257) (3-58) (-234-5)
Numerical values show the median and range. The symptomatic response data shows the number over the number tested and percentage in brackets .* Note that there is some missing data on symptomatic response therefore n=15 had triamcinolone and symptom data. BDR: bronchodilator reversibility;
FeNO: Fractional exhaled nitric oxide; FeNO
50
: Fractional exhaled nitric oxide at flow rate
50ml/second; FEV
1: forced expiratory volume in 1 second p
0.03
NS (0.7)
NS (0.7)
NS (0.9)
0.01
12
Table o Comparison between single and multiple allergies and each parameter response
Parameter Single allergy
(n=7)
Multiple allergies
(n=67)
Symptomatic response
FEV
1
(% pred)
BDR (%) pre
82
(45-88)
11
1/7 (14) post
74
(44-99)
13 change
13
(-41-21)
6
Pre
65
(27-109)
24
32/63 (51)
post
80
(38-106)
9 change
11
(-24-58)
-14
FeNO z score
FeNO
50
(ppb)
(0-25)
-0.6
(-1.9-4)
(11-20)
-0.6
(-1.9 to-0.9)
(-13-14)
-0.47
(-4-1.2)
(2-130)
-0.15
(-3.5-2.9)
(0-82)
-1.1
(-4.9-2)
(-126-23)
-1.2
(-5.3-1.1)
19
(8-257)
17
(8-23)
-7
(-234-9)
23
(6-123)
13
(2-79)
-11
(-89-33)
Numerical values show the median and range. The symptomatic response data shows the number over the number tested and percentage in brackets .
BDR: bronchodilator reversibility; FeNO: Fractional exhaled nitric oxide; FeNO
50
: Fractional exhaled nitric oxide at flow rate 50ml/second; FEV
1: forced expiratory volume in 1 second p
0.07
NS (0.6)
0.018
NS (0.4)
NS (0.7)
13
Graph a Log Fractional exhaled nitric oxide at flow rate 50ml/second pre and post triamcinolone
1000
100
10
1 pre post
Graph b Fractional exhaled nitric oxide at flow rate 250ml/second pre and post triamcinolone
30
20
10
0 pre post
14