Outcomes of Antibiotics in Adults with “Difficult to Treat” Asthma or the Overlap Syndrome

Figures & data

Table 1 Asthma Patient Characteristics at Baseline (Pre-Antibiotic Treatment)

Number of asthma patients audited	101
Age (years), mean (Sd)	55.6 (16.8)
Median, 25%ile-75%ile	59 (46–66)
Sex, no. M/F (% F)	35/66 (65.3)
Smoking status, n (%)
Never	62 (61.4)
Past	33 (32.7)
Current	6 (5.9)
(Self) referred from out of state, n (%)	17 (16.8)
Age of asthma onset (years),* mean (Sd)	33.9 (20.7)
Median, 25%ile-75%ile	32.8, 19–49
Child-onset (≤ age 12), n (%)	18 (18)
Adolescent-onset (12-≤18), n (%)	6 (6)
Adult onset (≥18), n (%)	76 (76)
Asthma symptom duration (years),* mean (Sd)	20.5 (16.9)
Median, 25%ile-75%ile	17.5, 6–30
Co-existing COPD diagnosis, n (%)	62 (61.4)
Asthma symptoms began after an acute respiratory illness,* n (%)	77 (77)
Number of exacerbations in year prior to baseline, n (%)*
0	40 (40)
1	44 (44)
≥2	16 (16)
Maximal Asthma Treatments (ever)
Taking inhaled corticosteroids (ICS), n (%)	83 (82.2)
Low dose ICS, n	80 (79.2)
Medium dose ICS, n	3 (3.0)
High dose ICS, n	0 (0)
Taking LABA and/or LAMA, n (%)	82 (81.2)
Taking Leukotriene receptor antagonist, n (%)	72 (71.3)
Taking a biologic, n (%)	5 (5.0)
Taking theophylline, n (%)	1 (1.0)
Taking chronic oral corticosteroids, n (%)	0 (0)
Pre-bronchodilator spirometry obtained, n (%)	74 (73.3)
FVC%predicted, mean (Sd)	85.2 (14.5)
Median, 25%ile-75%ile	86, 73–96
FEV1%predicted, mean (Sd)	80.9 (22.2)
Median, 25%ile-75%ile	87.5, 69–97
FEV1/FVC%predicted, mean (Sd)	73.2 (13.6)
Median, 25%ile-75%ile	76, 67–82
Diffusing capacity (DLCO) obtained, n (%)	62 (61.4)
Diffusing capacity (DLCO), mm/min/mmHg%predicted, mean (Sd)	93.2 (31.9)
Median, 25%ile-75%ile	91, 74–111
DLCO<80%predicted, n (%)	18 (29.0)
Post-bronchodilator spirometry obtained, n (%)	50 (49.5)
FVC%predicted, mean (Sd)	86.6 (14.5)
Median, 25%ile-75%ile	89, 77–98
FEV1%predicted, mean (Sd)	79.7 (21.3)
Median, 25%ile-75%ile	86, 68–95
Change from pre-bronchodilator FEV1%predicted, % (Sd)	6.5 (13.3)
Median change, 25%-75%ile, %	4.2, 1–11.4
Met ATS criteria† for reversible airway obstruction, n (%)	9 (18)
FEV1/FVC%predicted, mean (Sd)	71.3 (13.0)
Median, 25%ile-75%ile	74.5, 67–80
FEV1/FVC <70%, n (%)	16 (32.0)
Chlamydia pneumoniae (Cp) biomarkers
Cp IgG microimmunofluorescence (MIF) titer, n (%)*
<1:64	80 (80)
1:64	4 (4)
1:128	8 (8)
1:256	8 (8)
Cp IgA MIF titer, n (%)*
<1:16	94 (94)
1:16	2 (2)
1:32	1 (1)
1:64	1 (1)
1:128	2 (2)
Any Cp IgG≥1:64 and/or Cp IgA≥1:16, n (%)	25 (24.8%)
Mycoplasma pneumoniae (Mp) biomarkers
Mp IgM enzyme immunoassay (EIA) optical density (OD), n (%)**
≤0.9, negative	80 (80.8)
0.91–1.09, equivocal	5 (5.1)
≥1.1, positive	14 (14.1)
Mp IgG EIA OD, n (%)*
≤0.9, negative	23 (23)
0.91–1.09, equivocal	15 (15)
≥1.1, positive	62 (62)
Any Mp IgM≥1.1 and/or Mp IgG≥1.1, n (%)	67 (66.3)

Notes: *n=100, 1 case missing data. **n=99, 2 cases missing. †FEV1 variation of ≥12% and >200mL.

Table 2 Antibiotic Treatment Characteristics

Antibiotic(s) prescribed, n (%)	101 (100)
Azithromycin alone	31 (30.7)
Clarithromycin alone	2 (2.0)
Azithromycin and clarithromycin	2 (2.0)
Doxycycline alone	6 (5.9)
Minocycline alone	2 (2.4)
Azithromycin and doxycycline	49 (48.5)
Clarithromycin and doxycycline	7 (6.9)
Azithromycin and minocycline	2 (2.4)
Antibiotic treatment duration (months), mean (Sd)	12.8 (7.4)
Median, 25%ile-75%ile	12, 8–16
Months elapsed from baseline (pre-treatment) to follow-up, mean (Sd)	24.4 (11.3)
Median, 25%ile-75%ile	22, 14–35
Continuing to take antibiotics at follow-up, n (%)
Yes	52 (51.5)
No	49 (48.5)
Number of side effects reported at follow-up visits, n (%) (in 19 patients)	22 (21.8)
Mild, n (%)	16 (15.8)
Moderate, n (%)	5 (5.0)
Severe, n (%)	1 (1.0)
Discontinued due to side effect, n (%)	7 (6.9%)

Table 3 Clinical Outcomes After Taking Long-Term Antibiotics for Asthma: Controller Medication Use, Asthma Control, Severe Exacerbations and Self-Rated Quality of Life Improvement

Outcome	Baseline	Follow-Up	P-value*
Asthma Treatments
Taking inhaled corticosteroids (ICS), n (%)	69 (68.3)	35 (34.7)	<0.0001
Low dose ICS, n	67 (66.3)	34 (33.7)	<0.0001
Medium dose ICS, n	2 (2.0)	1 (1.0)	0.99
High dose ICS, n	0 (0)	0 (0)	1
Taking LABA and/or LAMA, n (%)	70 (69.3)	45 (44.6)	<0.001
Taking Leukotriene receptor antagonist, n (%)	63 (62.4)	48 (47.5)	<0.05
Taking a biologic, n (%)	1 (1.0)	1 (1.0)	1
Taking theophylline, n (%)	1 (1.0)	2 (2.0)	0.99
Taking chronic oral corticosteroids, n (%)	0 (0)	0 (0)	1
Asthma Control Test, mean score (Sd)	12.2 (4.5)	20.6 (3.9)	<0.0001**
Median, 25%ile-75%ile	11 (9–15)	21 (19–24)	<0.0001†
Well controlled (ACT score≥20), n (%)	10 (9.9)	71 (70.3)	<0.0001
Sub-optimally controlled (16–19), n (%)	12 (11.9)	1 (15.8)	0.004
Severely uncontrolled (≤15), n (%)	79 (78.2)	14 (13.9)	<0.0001
One or more severe exacerbations in the previous 4 weeks, n (%)^¶	51 (50.5)	18 (17.8)	<0.0001
One or more oral steroid bursts >3d, n (%)	48 (47.5)	18 (17.8)	<0.0001
One or more hospitalizations for asthma, n (%)	19 (18.8)	0 (0)	<0.0001
Quality-of-life improvement self-assessment at follow-up
Unchanged		13 (12.9)
Some better		21 (20.8)
Much better		26 (25.7)
Very much better		41 (40.6)

Notes: *Fishers Exact test unless indicated otherwise. **Paired t-test. †Mann–Whitney U-test. ^¶Subcategories sum to >73 because a severe exacerbation may include both subcategories.

Figure 1 Asthma Control Test (ACT) scores (Y-axis) for individual patients (X-axis) at baseline (before antibiotic treatment: blue bars) and at follow-up (red bars). Asterisks (*) indicate patients with follow-up ACT scores of 25 who are no longer taking antibiotics.