J Vet Intern Med 2007;21:149–156
Effects of Genetic and Environmental Factors on Chronic Lower
Airway Disease in Horses
Alessandra Ramseyer, Claude Gaillard, Dominik Burger, Reto Straub, Ursula Jost, Cornel Boog,
Eliane Marti, and Vincent Gerber
Background: Environment and genetics influence the manifestation of recurrent airway obstruction (RAO), but the
associations of specific factors with mild, moderate, and severe clinical signs are unknown.
Hypothesis: We hypothesized that sire, feed, bedding, time outdoors, sex, and age are associated with clinical manifestations
of mild, moderate, and severe lower airway disease.
Animals: Direct offspring of 2 RAO-affected Warmblood stallions (F1S1, n 5 172; F1S2, n 5 135); maternal half-siblings of
F1S1 (mHSS1, n 5 66); and an age-matched, randomly chosen control group (CG, n 5 33).
Methods: A standardized questionnaire was used to assess potential risk factors and to establish a horse owner assessed
respiratory signs index (HOARSI 1–4, from healthy to severe) according to clinical signs of lower airway disease.
Results: More F1S1 and F1S2 horses showed moderate to severe clinical signs (HOARSI 3 and HOARSI 4 combined, 29.6
and 27.3%, respectively) compared with CG and mHSS1 horses (9.1 and 6.2%, respectively; contingency table overall test, P ,
.001). Sire, hay feeding, and age (in decreasing order of strength) were associated with more severe clinical signs (higher
HOARSI), more frequent coughing, and nasal discharge.
Conclusions and Clinical Relevance: There is a genetic predisposition and lesser but also marked effects of hay feeding and
age on the manifestation of moderate to severe clinical signs, most markedly on coughing frequency. In contrast, mild clinical
signs were not associated with sire or hay feeding in our populations.
Key words: Equine; Genetics; Lung; Recurrent airway obstruction.
quine recurrent airway obstruction (RAO), or
heaves, is likely a polygenetic and multifactorial
disorder. RAO is characterized by clinically evident
increased breathing effort, coughing, and airway hyperreactivity, as well as neutrophil and mucus accumulation
in the airways.1–3
The former terms chronic obstructive pulmonary
disease (COPD) and chronic bronchitis/bronchiolitis have
been used to describe a spectrum of equine chronic lower
airway diseases, including RAO and inflammatory airway
disease (IAD). The incidence of RAO seems to be related
to environmental factors, such as type of hay feeding,
straw bedding, housing, and time horses can spend
outdoors.1,3–6 IAD also is a chronic respiratory disease,
but affected horses exhibit clinical signs that are much
milder than RAO. In contrast to RAO, the pathogenesis
of IAD is less well understood. Environmental, genetic,
and infectious factors have been proposed.7
A familial predisposition for equine chronic lower
airway disease was first described by Schaeper8 in 1939.
He reported that 14 of 27 offspring from the heavesaffected stallion ‘‘Egmont’’ became affected and that
several mares with heaves mated to unaffected stallions
produced affected female descendants, which on their
part produced affected offspring. Other investigators
E
From the Equine Clinic (Ramseyer, Straub, Jost, Boog, Gerber),
Division of Clinical Research (Burger, Marti), Department of
Clinical Veterinary Medicine, Institute of Genetics (Gaillard),
Vetsuisse-Faculty, University of Berne, Bern; and the National Stud,
Avenches (Burger, Marti), Switzerland.
Reprint requests: V. Gerber, PD, Dr med vet, PhD, DACVIM,
DECEIM, FVH, Vetsuisse-Fakultät Universität Bern, Departement
für klinische Veterinärmedizin, Pferdeklinik, Länggass-Strasse 124,
CH-3012 Bern, Switzerland; e-mail: [email protected].
Submitted October 28, 2005; Revised February 13, 2006; April 7,
2006; Accepted July 18, 2006.
Copyright E 2007 by the American College of Veterinary Internal
Medicine
0891-6640/07/2101-0021/$3.00/0
report similar familial occurrences of chronic lower
airway disease.9,10 These reports, however, did not
include control groups. The only comprehensive investigation on the genetic background of equine chronic
lower airway disease, by Marti et al,11 investigated the
genetic influence on chronic obstructive bronchitis in
different breeds. They reported disease status of the
parent, dustiness of the environment, and age as
important factors.
The aims of this study were to assess factors that have
an influence on clinical manifestations of mild, moderate, and severe lower airway disease (ie, coughing, nasal
discharge, abnormal breathing pattern, reduced performance). The genetic effect of the sire; the environmental
effects of feed, bedding, and time outdoors; sex; and age
were investigated in direct offspring of 2 affected sires,
a group of half-siblings, and a control group.
Materials and Methods
Questionnaire
A standardized questionnaire was developed (Table 1). The
occurrence of clinical signs and the management practices were
assessed over the entire time horses were kept by the owner.
Owners were interviewed by 2 veterinarians and 1 veterinary
student, all trained for consistency of the questionnaire interviews.
Based on the respiratory signs reported by the owner (eg, coughing,
nasal discharge, poor performance, abnormal breathing) horses
were classified into 1 of the 4 horse owner assessed respiratory signs
index (HOARSI) categories (Table 2). The questionnaire used for
owner interviews included more detailed questions, but data had to
be categorized for statistical analyses (ie, owners were asked to
describe the frequency of coughing). Based on this description, the
interviewer categorized coughing as the following: occasional
(intermittent coughing with periods without cough of 1 week or
more), regular (horses coughing consistently at least every week but
no more than once a day), or frequent (horses coughing every day,
several times). HOARSI, cough, nasal discharge, performance,
bedding, feed, and time outdoors, used in the statistical analyses and
reported here, all referred to the time when the horse exhibited the
150
Ramseyer et al
Table 1.
Owner’s questionnaire.
Question
Classification of Answer
Time horse owned
Frequency of coughingb
Mucous nasal discharge after exerciseb
Abnormal breathing at rest, during, or after exerciseb
Subjective performanceb
Seasonal occurrence of symptoms
(combinations of seasons possible)
Contact with other horses or contact with donkeys
Turn-out time (paddock/pasture)
Bedding type
Feeding (roughage type)
Disease prevention
Use of the horse
a
b
Codea
No. of years
Absent
Occasional
Regular
Frequent
Absent
Present
Absent
Present
Excellent
Good
Satisfactory
Poor
Nonseasonal
Spring
Summer
Fall
Winter
Present/absent
Present/absent
Never/infrequent
Frequent/daily
Constant
Straw
Other (wood shavings/hemp, etc.)
Hay
Hay in combination with another roughage (silage, straw,
hay pellets)
Hay modified (wet hay, hay pellets)
No hay (haylage, silage)
Frequency and type of vaccinations and deworming
Show jumping, dressage, leisure, breeding, etc.
4
3
2
1
2
1
2
1
4
3
2
1
1
2
3
1
2
1
2
3
4
Code for statistical evaluation in logistic regression.
Answers used in definition of horse owner assessed respiratory signs index.
most severe disease manifestation. Also, clinical signs must have
persisted over a minimum of 2 months. For historically healthy
horses who never showed clinical signs and also when owners were
unable to clearly define a time of worst signs, information from the
most recent 2-month period was recorded. All horses had a longer
than 2-month history of hay feeding in their life.
Horses
Horses in this study were Swiss Warmblood horses, over 5 years
of age, bred and housed in Switzerland, and registered with the
Swiss Equestrian Federation. Two influential stallions (S1 and S2),
with a confirmed history of RAO, and a large number of their
descendants, were chosen for the study. We then searched for all
direct offspring. Owner addresses were available for 256 descendants of S1 and 175 descendants of S2; all were called;
approximately 70% could be reached, had the necessary information, and agreed to participate. Four groups of horses were
investigated: first-generation descendants of S1 (F1S1, n 5 172);
first-generation descendants of S2 (F1S2, n 5 135); control group
(CG, n 5 33), age matched to F1S1, otherwise randomly selected;
and maternal half-siblings (mHSS1; n 5 66) of S1 progeny from
Table 2. Horse owner assessed respiratory signs index (HOARSI): scoring system created to classify horses
according their clinical signs of lower airway disease.
HOARSI
1
2
3
4
a
Clinical Signs
No episodes of coughing or nasal discharge
Mucous nasal discharge, occasional coughing, or both
Abnormal breathing, regular or frequent coughing,
or both
Abnormal breathing, regular or frequent coughing
accompanied by poor performance, or bothb
Severity of Lower Airway Disease
Codea
No clinical signs of respiratory disease
Mild clinical signs of respiratory disease
4
3
Moderate clinical signs of respiratory disease
2
Severe clinical signs of respiratory disease
1
Code for statistical evaluation in logistic regression.
Performance was only taken into account when judged as poor and when in combination with abnormal breathing, regular or frequent
coughing, or both.
b
Genetics of Equine Chronic Lower Airway Disease
151
Table 3. Sex, age, and use distribution of study population (n 5 406) for direct descendants of stallion 1 (F1S1);
direct descendants of stallion 2 (F1S2); an age-matched, otherwise randomly chosen control group (CG); and
maternal half-siblings (mHSS1) of stallion 1 descendants.
Groups
Number
Sex (male/female) (%)
Mean age (years)
Age class (%)
4
3
2
1
F1S1
F1S2
CG
mHSs1
172
54.1/45.9
10.9
135
43.0/57.0
9.9
33
45.5/54.5
10.0
66
37.9/62.1
10.3
(5–7 years)a
(8–10 years)a
(11–13 years)a
(.13 years)a
7.0
35.5
49.4
8.1
6.7
57.0
36.3
0.0
15.1
45.5
36.4
3.0
25.8b
30.3
21.2
22.7b
47.1
20.4b
6.4
25.0
1.2
54.8
6.7
8.9
28.1
1.5
45.4
3.0
9.1
36.4
6.1
51.5
12.1
7.6
24.2
4.6
Use (%)
Jumping
Dressage
Endurance/driving/eventing
Leisure
Breeding
a
b
Numerical code that was used in statistical analyses.
Significantly different from other groups.
53 mares and by 12 different sires. The respiratory health of
dams and sires (other than S1 and S2) did not influence inclusion in
the study.
Statistical Analyses
Questionnaire information was categorized numerically (Tables 1, 2). Descriptive and test statistics were performed with the
software package SAS.a Chi-square statistics were applied to test
hypotheses of contingency tables (PROC FREQ).
The different severity classes of the respiratory conditions were
treated as ordinal response variables and were modeled as
cumulative logit functions by performing an ordered logistic
regression with the proportional odds model.12 The SAS procedure
PROC GENMOD was applied for this analysis. The following
model was used: logit (respiratory status) 5 a + bixi + ej, where a is
the intercept, bi is the partial regression coefficient of the i-th
independent variable, xi is the i-th independent variable (group, sex,
feeding, bedding, time outdoors, age class [5–7, 8–10, 11–13, and
.13 years of age]), and ej is the error of the j-th horse. P values for
the odds ratios with 95% confidence intervals (CI) are reported.
Significance level was set at P # .05.
Results
Description of Horse Populations
The entire sample size consisted of 406 horses. The
difference among the average ages of the 4 groups was
significant (P 5 .003) but small (Table 3). The distribution
in the 4 age classes was better balanced in the mHSS1
group than in the others. Use (P 5 .04) but not sex ratios
(P 5 .087) showed a significant difference among groups.
Environmental Factors
In all groups, the majority of the horses were fed hay
(42–56%), and more than a third were fed hay in
combination with another roughage (33–39%; Fig 1A).
Less than 10% were fed wet hay or hay pellets (3–9%),
and the remainder were fed haylage or silage (6–15%).
Approximately 84% of horses were bedded on straw,
and the others were on a litter other than straw (eg,
shavings, hemp, or other bedding). Seventy-three
percent of the horses had regular access to a paddock
or a pasture, 24% had unlimited access, and only 3% had
restricted or no outdoor access. No significant differences in feeding, bedding types, and time outdoors
among groups were found (P 5 .28, P 5 .47, P 5 .26,
respectively).
Clinical signs
HOARSI. Overall, 8.6% horses showed severe clinical
signs (HOARSI 4), 14.5% showed moderate clinical
signs (HOARSI 3), and 23.6% were reported to show
only mild respiratory signs (HOARSI 2) of lower airway
disease. Owners of 53.2% horses reported their horses as
healthy (HOARSI 1).
Descriptive statistics showed higher prevalences of
HOARSI 4 and HOARSI 3 cases in F1S1 and F1S2
horses compared with CG and mHSS1 horses (contingency tables overall test, P , .001; Fig 1B). The
occurrence of mild symptoms of lower airway disease
(HOARSI 2), however, did not differ much among
groups: 24.4% of F1S1, 24.4% of F1S2, 27.4% of CG,
and 18.2% of mHSS1 were classified as HOARSI 2.
For 16.7% of all horses with a HOARSI 2, an age was
specified by the owners as to when the most severe
clinical signs were observed: age 8 6 2.4 years (mean 6
standard deviation [SD]). For 69.1% of all horses with
HOARSI 3 or HOARSI 4, a mean age of worst
symptoms was specified by the owners, also 8 6
2.4 years. For mHSS1 and CG horses, a year of worst
symptoms was only specified in 3 individuals.
In addition, owners were asked about a seasonal
occurrence or an exacerbation of clinical signs. Forty-
152
Ramseyer et al
Fig 1. Distribution of environmental factors, feeding and bedding (A), horse owner assessed respiratory signs index (HOARSI)
(B), and frequency of coughing (C) in direct descendants of stallion
1 (F1S1); direct descendants of stallion 2 (F1S2); an age-matched,
otherwise randomly chosen control group (CG); and maternal halfsiblings (mHSS1) of stallion 1 descendants.
five percent of 190 horses with HOARSI 2–4 were
reported to show seasonality: 40 in spring, 12 in
summer, 2 in fall, 19 in winter, 4 in spring and summer,
8 in spring and fall, and 1 in summer and winter. Among
horses with seasonal signs in summer, spring and
summer, and summer and winter (total n 5 17), almost
all showed moderate and severe clinical signs (8 with
HOARSI 3, 8 with HOARSI 4).
Neither bedding nor time outdoors were associated
with HOARSI, but the severity of lower airway disease
was significantly influenced by group, feeding regimen,
and age (P , .001, P , .001, P 5 .002, respectively).
Results with the reduced model (without bedding and
time outdoors) are presented as odds ratios (Figs 2–4).
Group. Group data are shown in Fig 2A. F1S1 horses
had a 4.1 times higher odds ratio to be affected by more
severe clinical signs of lower airway disease compared
with mHSS1 (CI 2.0–8.2, P , .001). F1S2 horses had 5.5
(CI 2.6–11.4, P , .001), and 2.2 (CI 1.0–4.8, P 5 .05)
Fig 2. Group effect (direct descendants of stallion 1 [F1S1]; direct
descendants of stallion 2 [F1S2]; an age-matched, otherwise
randomly chosen control group [CG]; and maternal half-siblings
[mHSS1] of stallion 1 descendants) on horse owner assessed
respiratory signs index (HOARSI) (A), coughing frequency (B),
and nasal discharge (C) shown as odds ratios with 95% confidence
intervals. +: P , .001, *: P , .05, u: P , .1. Exact P values are
given in the text.
times higher odds ratios to show more severe clinical
signs of respiratory disease compared with the mHSS1
group and CG group, respectively. Significant differences in odds ratios were not found when F1S1 horses
and F1S2 horses (P 5 .21) or when mHSS1 horses and
CG horses (P 5 .06) were compared. Even though
HOARSI 4 were reported 4 times more often in F1S1
horses than in CG horses (Fig 1A), the odds ratios of
higher HOARSI scores were not significantly different
between these 2 groups (P 5 .19).
Age. Age data are shown in Fig 3A. Horses older than
13 years of age had 2.8 (CI 1.2–6.4, P 5 .017) and 5.8
(CI 2.0–16.8, P 5 .001) higher odds ratios for severe
respiratory signs compared with horses between 8–10
and 5–7 years of age. Horses 11–13 years of age had 1.5
(CI 1–2.3, P 5 .04) and 3.2 (CI 1.3–7.3, P 5 .006) higher
Genetics of Equine Chronic Lower Airway Disease
Fig 3. Age effect (in years) on horse owner assessed respiratory
signs index (HOARSI) (A), coughing frequency (B), and nasal
discharge (C) shown as odds ratios with 95% confidence intervals.
+: P , .001, *: P , .05, u:P , .1. Exact P values are given in
the text.
odds ratios to exhibit severe clinical signs than horses 8–
10 and 5–7 years of age. No significant differences in
odds ratios were found when horses .13 years of age
and horses aged 10–13 years (P 5 .16), as well as when
horses aged 8–10 years and horses aged 5–7 years (P 5
.08) were compared.
Feeding. Feeding data are shown in Fig 4A. Horses
fed hay had 3.0 (CI 1.9–4.7, P , .001) and 3.3 (CI 1.6–
6.8, P 5 .002) times higher odds ratios for more severe
signs of lower airway disease compared with horses fed
hay and another roughage and horses fed haylage. The
odds ratio to exhibit severe clinical signs of horses fed
hay and other roughage were decreased to 0.4 times that
of horses fed wet hay (CI 0.2–0.9, P 5 .02). Horses fed
wet hay had a 2.8 times higher odds ratio to show more
severe clinical signs of lower airway disease compared
with horses fed haylage (CI 1.1–7.3, P 5 .039). No
153
Fig 4. Feeding effect on horse owner assessed respiratory signs
index (HOARSI) (A), coughing frequency (B), and nasal discharge
(C) shown as odds ratios with 95% confidence intervals. Hay+: hay
in combination with another roughage. +: P , 0.001, *: P , .05.
Exact P values are given in the text.
significant odds ratios were found for comparisons of
hay with wet hay (P 5 .66) and hay in combination with
another roughage with haylage (P 5 .82).
Coughing. Overall, only 4% of the horses showed
frequent coughing, 14% showed regular, and 23%
occasional coughing, whereas 59% never coughed.
Frequent, regular, and occasional coughing all were
increased in F1S1 and F1S2 horses compared with
mHSS1 and CG (contingency table overall test, P ,
.001). Coughing was significantly influenced by group,
feeding, and age (P , .001, P , .001, P 5 .005,
respectively).
Group. Group data are shown in Fig 2B. The odds of
coughing were reduced by almost half in F1S1 horses
(odds ratio 0.6, CI 0.4–1.0, P 5 .036) relative to F1S2
horses. The comparison between F1S1 and mHSS1
154
Ramseyer et al
identified a 4.5 higher odds ratio (CI 2.1–9.7, P , .001)
for worse coughing in F1S1. F1S1 horses also had a 2.9
higher odds ratio for more frequent coughing than did
CG horses (CI 1.2–7.1, P 5 .02). F1S2 horses had 7.3fold (CI 3.2–16.4-fold; P , .001) and 4.7-fold (CI 1.9–
11.8-fold, P , .001) higher odds ratios for more frequent
coughing than did mHSS1 and CG, respectively. No
significant (P 5 .44) difference in odds ratio was found
for the comparison of HSS1 and CG for coughing.
Age. Age data are shown in Fig 3B. Horses .13 years
of age had 2.5-fold (CI 1.1–6.1-fold, P 5 .36) and 5.7fold (CI 1.8–18.8-fold, P 5 .004), respectively, increased
odds ratios for increased frequency of coughing
compared with horses aged 8–10 years and horses aged
5–7 years. Horses aged 11–13 years had 1.5-fold (CI
1.0–2.4-fold, P 5 .05) and 3.5-fold (1.3–9.2-fold, P 5
.01), respectively, higher odds ratios than did horses
aged 8–10 years and horses aged 5–7 years. No significant differences in odds ratios were found when horses
.13 years of age were compared with horses aged 11–
13 years (P 5 .26) and when horses aged 8–10 years
were compared with horses aged 5–7 years (P 5 .098).
Feeding. Feeding data are shown in Fig 4B. Horses
fed hay had 2.5-fold (CI 1.5–3.9-fold; P , .001) and 2.5fold (CI 1.2–5.3-fold; P 5 .01) higher odds ratios than
did horses fed hay in combination with another
roughage and horses fed haylage, respectively. No
significant differences in odds ratios were found for
the comparisons of dry hay with wet hay (P 5 .69),
haylage with hay in combination with another roughage
(P 5 .93), and wet hay with haylage (P 5 .12), as well as
when hay in combination with another roughage was
compared with wet hay (P 5 .067).
Nasal Discharge. Overall, nasal discharge was present
in 35% of the study population. Forty-three percent of
F1S1, 33% of F1S2, 67% of CG, and 20% of mHSS1
were reported to show nasal discharge after exercise.
Nasal discharge was significantly influenced by group (P
5 .004), feeding regimen (P , .001), and age (P 5 .007).
Group. Group data are shown in Fig 2C. F1S1 had
a 3.7 times higher odds ratio (CI 1.7–8.1, P , .001) for
the presence of nasal discharge compared with mHSS1.
F1S2 horses had a 2.9 times higher odds ratio than did
mHSS1 horses (CI 1.3–6.5, P 5 .12); the odds ratio for
the presence of nasal discharge of mHSS1 horses was
decreased to 0.3 times that of the CG group (CI 0.1–0.9,
P 5 .029). No significant differences in odds ratios were
found when F1S1 horses and CG horses (P 5 .68) and
F1S2 horses and CG horses (P 5 .82) were compared, as
well as when F1S1 horses were compared with F1S2
horses (P 5 .29).
Age. Age data are shown in Fig 3C. Horses older than
13 years of age had 3.5-fold (CI 1.4–9.1-fold, P 5 .01),
3.7-fold (CI 1.5–9.6-fold, P 5 .006), and 7.2-fold (CI 2.2–
23.2-fold, P 5 .001) higher odds ratios, respectively, for
nasal discharge than did horses aged 11–13 years, horses
aged 8–10 years, and horses 5–7 years of age. No
significant differences in odds ratios were found when
horses 11–13 years of age were compared with horses
aged 8–10 years (P 5 .79) or aged 5–7 years (P 5 .13), as
well as when 8–10-year-old horses were compared with 5–
7-year-old horses (P 5 .16).
Feeding. Feeding data are shown in Fig 4C. Horses
fed hay had 2.6-fold (CI 1.6–4.4-fold, P , .001) and 2.5fold (CI 1.1–5.6-fold, P 5 .03) higher odds ratios for
nasal discharge than did horses fed hay in combination
with another roughage and horses fed haylage, respectively. The odds ratio for nasal discharge of horses
fed hay and other roughage was decreased to 0.4 times
(CI 0.2–0.9-fold, p5.036) that of horses fed wet hay. No
significant differences in odds ratios were found for the
comparisons of hay with wet hay (P 5 .95), hay in
combination with another roughage with haylage (P 5
.89), and wet hay with haylage (P 5 .11).
Performance. Overall, 5.2% of horses showed poor,
8.9% showed satisfactory, 34.7% showed good, and
51.2% showed excellent performance. There were no
significant differences of performance pattern among
groups (P 5 .31). A significant influence of sex (P 5 .04)
on performance was found: male horses performed
better. Group (P 5 .63), feeding (P 5 .09), bedding (P 5
.47), time spent outdoors (P 5 .91), and age (P 5 .65)
did not influence performance capacity.
Abnormal Breathing Pattern. Abnormal breathing
pattern, variably described by owners as ‘‘heaving,’’
‘‘shortness of breath,’’ or ‘‘increased breathing effort,’’
was present in only 12.6% of horses. Overall, 16.8% of
the F1S1 group, 10% of the F1S2 group, 9% of the CG
group, and 9% of the mHSS1 group had abnormal
breathing patterns. Seventy-five percent of HOARSI 4,
31% of HOARSI 3, 4% of HOARSI 2, and only 1% of
HOARSI 1 horses were reported to breathe abnormally.
Furthermore, coughing frequency was (P , .001)
correlated with abnormal breathing. Abnormal breathing was reported more often in horses who showed
frequent (68.8%) and regular (33.9%) coughing than in
horses with occasional (16.8%) or absent (2.1%) coughing. Logistic regression identified significant associations
of abnormal breathing with feeding (P 5 .003) and age
(P 5 .016) but not with sex (P 5 .31), group (P 5 .81),
bedding (P 5 .094), and time spent outside (P 5 .89).
Discussion
Based on our findings, the reported familial risk for
equine chronic lower airway disease8–11 can now be more
specifically defined as a risk for moderate to severe
clinical signs, in particular for increased coughing. Marti
et al11 previously showed significant associations of
disease status of the parents, environment, and age with
chronic lower airway disease in the horse. We investigated
these factors in more detail on a larger number of horses
by using a comprehensive questionnaire. Based on the
Genetics of Equine Chronic Lower Airway Disease
owner-assessed information, we cannot definitively diagnose lower airway disease or clearly differentiate
between RAO and IAD. Nevertheless, the chronicity of
clinical signs (Table 2) and low prevalence of chronic
infectious and neoplastic lower airway diseases in
Switzerland13 suggest that the moderate to severe clinical
signs of HOARSI 3 and HOARSI 4 are largely consistent
with RAO. The milder signs of HOARSI 2 are likely
consistent with IAD.7 Importantly, however in our study
these milder clinical signs were reported in older
‘‘occasional coughers’’ (age of worst signs was reported
in relatively few HOARSI 2 animals but was similar to
HOARSI 3 and HOARSI 4) and, therefore, cannot be
compared directly with IAD in racehorses.
We expected to find a significant number of HOARSI
3 and HOARSI 4 cases that would be atypical for RAO
but found only 2 horses with a history that was
consistent with summer pasture associated obstructive
pulmonary disease14 and 2 horses without seasonal signs
who no longer responded to hay removal. The latter 2
horses have since been comprehensively examined and
diagnosed as severe, unresponsive RAO (possibly with
emphysema), without radiographic evidence for interstitial pneumonia or bronchiectasis. Furthermore, all
horses who were reported to be in contact with donkeys
belonged to the healthy HOARSI 1 group, removing
a main potential etiologic confounder, the lungworm
Dyctiocaulus arnfieldi, from consideration.
Our study population overall lived under very similar
environmental conditions (Fig 1A), without major confounding feeding, bedding, or age differences among
groups. The main drawbacks of using owner assessment
of clinical disease severity are misclassification and recall
bias. For instance, more severe signs are easier to
recognize and recall than milder signs. Rechecks over
6 months later of approximately 10% of the interviewed
owners, however, revealed a high consistency of
categorization. Furthermore, we had a favorable return
rate of over 70%. It is still possible that nonrespondents
introduced a bias (ie, severely affected horses may have
been sold or euthanized). Alternatively, owners of
healthy animals could have been less willing to take
the time for the interview. Because the distribution of
nonrespondents was even across groups, this would have
minimally influenced our results.
Moderate to severe clinical signs were observed in
almost a third of S1 and S2 offspring but only in less
than 1 of 10 maternal half-sibling and random controls
(Fig 1B). The 2- to 5-fold increased risk for moderate to
severe clinical signs (Fig 2A) is in the range previously
reported for equine COPD: 3.2-fold when 1 (regardless
of whether dam or sire) and 4.6-fold increased risk when
2 parents are affected.11 In contrast, HOARSI 2
frequency (Fig 1B) was very similar in all groups,
indicating no genetic basis for mild clinical signs in our
study. Although we cannot exclude a genetic basis for
the still rather poorly defined syndrome IAD, our data
suggest that the ‘‘chronic occasional, older cougher’’
phenotype is likely to be the result of pathogenetic
mechanisms that differ from those underlying more
severe disease, such as RAO.
155
When we analyzed clinical signs as separate
end points, coughing emerged as the most distinctly
heritable characteristic, showing considerably higher
sire-associated odds ratios than nasal discharge (Fig 2B
versus Fig 2C). Increased airway reactivity has been
reported in RAO-affected animals15,16 and can underlie
a familial predisposition in human asthma.17,18 Airway
hyperreactivity could be a genetically determined
trait, leading to coughing and increased severity of
clinical signs in HOARSI 3 and 4 horses of our study
population.
The observed age associations with HOARSI, coughing, nasal discharge, and abnormal breathing pattern
(Figs 3A–C) and the absence of a male versus female sex
predilection agree with previous studies.2,5,11,19 Hay
feeding has long been considered a major risk factor,3
and eliminating hay from the diet is the mainstay of
RAO therapy.4 In our study, odds ratios for hay feeding
were most markedly and consistently increased for
HOARSI, coughing frequency, and nasal discharge
compared with haylage (Fig 4A–C). Haylage feeding,
which has been shown to improve clinical signs of RAO6
showed the lowest risk for increased disease severity of
all roughage feeds. In contrast, risk of hay feeding was
not significantly different compared with feeding of wet
hay. This finding indicates that wetting hay should not
be recommended as a general management practice for
RAO-affected horses. Importantly, however, feeding
type did not appear to influence the frequency of milder
signs of HOARSI 2 (results not shown). This observation is in accordance with our recent findings that hay
compared with haylage feeding caused neutrophilic
inflammation but no clinical signs in horses with
a history of IAD.b
Environmental factors other than hay feeding, such as
straw bedding, housing, and time horses can spend
outdoors1,3–6 also have been proposed as risk factors for
lower airway disease in horses. Surprisingly, these other
environmental factors showed no significant associations
with HOARSI, coughing, nasal discharge, or breathing
patterns reported by the owners. For statistical reasons,
categorization of these environmental factors was relatively broad (Table 1). Turn-out time was particularly
difficult to categorize because very few horses in Switzerland have turn-out that is consistent. Many horses in our
study had free access to individual small paddocks built
adjacent to the stall, others had seasonal and weatherdependent pasture access. Therefore, it was not possible to
accurately assess the large variability in dust exposure for
the majority of the investigated horses. In a previous
study, we found a significant effect of the stable
environment, when stables were visited and air quality
was subjectively graded as poor, satisfactory, or good.11
The chosen categories in the present study allowed for the
most consistent classification but may have been too
broad and the sample size of the category ‘‘no outdoor
access’’ too small to identify an effect of turn-out time.
Possibly, analysis of even larger numbers of affected
versus healthy animals would allow for more detailed
categorization and could thus identify more subtle
associations.
156
Ramseyer et al
In conclusion, there is a strong genetic predisposition
and lesser but also marked associations of hay feeding
and age with the manifestation of moderate to severe
signs of chronic lower airway disease. In contrast, milder
clinical signs did not appear to be influenced by heritable
effects or hay feeding in the studied populations.
Practical recommendations must be formulated with
caution, but, based on these results, we propose that
RAO be considered a criterion of heritability soundness
in breeding stallions, because breeding to an affected sire
significantly increases the risk of moderate to severe
chronic lower airway disease in the offspring. Alternatively, hay feeding should be avoided in offspring from
RAO-affected parents if the development of severe lower
airway disease is to be prevented.
Footnotes
a
Worldwide Headquarters, SAS Institute Inc, 100 SAS Campus
Drive, Cary, NC 27513 2414, USA
b
Boog C, Ramseyer A, Widmer A, et al. Benefits of feeding
haylage instead of hay for upper and lower airway health in
horses affected with inflammatory airway disease. World Equine
Airway Symposium, July 20–22, 2005, Ithaca, NY, Cornell
University. Published by Cornell University Press
Acknowledgments
We thank Director P. A. Poncet of the Swiss National
Stud for his invaluable help and all the horse owners for
their participation. This study was funded by Vetsuisse
and DKV grants and the Berne Equine Lung Research
Group.
References
1. Robinson NE, Derksen FJ, Olszewski MA, et al. The
pathogenesis of chronic obstructive pulmonary disease of horses.
Br Vet J 1996;152:283–306.
2. Gerber H. Chronic pulmonary disease in the horse. Equine
Vet J 1973;5:26–33.
3. Lowell FC. Observation on heaves. An asthma like syndrome
in the horse. J Allergy 1964;35:322–330.
4. Schatzmann U, Straub R, Gerber H, et al. Elimination of hay
and straw as a therapy for chronic lung diseases in the horse.
Tierarztl Prax 1974;2:207–214.
5. McPherson EA, Lawson GH, Murphy JR, et al. Chronic
obstructive pulmonary disease (COPD): Factors influencing the
occurrence. Equine Vet J 1979;11:167–171.
6. Vandenput S, Votion D, Duvivier D, et al. Effect of a set
stabled environmental control on pulmonary function and airway
reactivity of COPD affected horses. Vet J 1998;155:189–195.
7. International Workshop on Inflammatory Airway Disease:
Defining the Syndrome. Proceedings of Workshop in Boston,
October 2002. Eq Vet Educ 2003;15(1):61–63.
8. Schaeper W. Investigation on the heritability and the nature
of heaves in the horse. Tieraerztl Rundschau 1939;31:595–599.
9. Koch P. Heredity of chronic alveolar emphysema of the lungs
in horses. Dtsch Tierarztl Wochenschr 1957;64:485–486.
10. Gerber H. The genetic basis of some equine diseases (Sir
Frederick Hobday Lecture). Equine Vet J 1989;21:244–248.
11. Marti E, Gerber H, Essich G, et al. The genetic basis of
equine allergic diseases. 1. Chronic hypersensitivity bronchitis.
Equine Vet J 1991;23:457–460.
12. McCullagh P. Regression models for ordinal data (with
discussion). J R Stat Soc [Ser B] 1980;42:109–142.
13. Bracher V, von Fellenberg R, Winder C, et al. An
investigation of the incidence of chronic obstructive pulmonary
disease (COPD) in random populations of Swiss horses. Equine
Vet J 1991;23:136–141.
14. Seahorn TL, Beadle RE, McGorum BC, et al. Quantification of antigen-specific antibody concentrations in tracheal lavage
fluid of horses with summer pasture-associated obstructive
pulmonary disease. Am J Vet Res 1997;58:1408–1411.
15. Hoffman AM, Mazan MR, Ellenberg S. Association
between bronchoalveolar lavage cytologic features and airway
reactivity in horses with a history of exercise intolerance. Am J Vet
Res 1998;59:176–181.
16. Derksen FJ, Robinson NE, Armstrong PJ, et al. Airway
reactivity in ponies with recurrent airway obstruction (heaves).
J Appl Physiol 1985;58:598–604.
17. Koh YY, Kang EK, Kang H, et al. Bronchial hyperresponsiveness in adolescents with long-term asthma remission: Importance of a family history of bronchial hyperresponsiveness. Chest
2003;124:819–825.
18. Longo G, Strinati R, Poli F, et al. Genetic factors in
nonspecific bronchial hyperreactivity. An epidemiologic study. Am
J Dis Child 1987;141:331–334.
19. Dixon PM, Railton DI, McGorum BC. Equine pulmonary
disease: A case control study of 300 referred cases. Part 2: Details
of animals and historical and clinical findings. Equine Vet J
1995;27:422–427.