Partial Resolution of Hypoplastic Trachea in Six English Bulldog Puppies with Bronchopneumonia

Introduction

Brachycephalic airway syndrome is a combination of nasal and oropharyngeal anatomic abnormalities resulting from selective breeding to reduce the length of the maxilla without concurrent reduction in the soft tissue of the nose, palate, and pharynx.^1,2 The resulting excess of soft tissue causes airway obstruction in affected animals, with clinical signs that may include inspiratory stertor and stridor, exercise and heat intolerance, cyanosis, and respiratory distress. The primary abnormalities of brachycephalic airway syndrome are stenotic nares and an overlong soft palate. Secondary changes that occur as a result of chronic airway obstruction include eversion of the mucosa of the laryngeal ventricles (everted laryngeal saccules), pharyngeal edema, and laryngeal collapse. Additional reported respiratory tract abnormalities in brachycephalic dogs include bronchial collapse, bronchial stenosis, amygdalitis, maccoglossia, reduced buccal opening, nasopharyngeal collapse, nasopharyngeal turbinates, epiglottic cysts, and laryngeal granulomas.^1–7

Tracheal hypoplasia is a concurrent finding in many patients with brachycephalic airway syndrome.^1–3,5–13 Affected dogs have small tracheal cartilage rings with overlapping ends and a narrow or absent dorsal tracheal membrane.^{1,8,10,13–16} Tracheal hypoplasia typically involves the whole trachea, with a uniformly narrowed lumen from the larynx to the carina. English bulldogs are more commonly affected by tracheal hypoplasia than other breeds.^1,8,13–18 Tracheal hypoplasia is a congenital trait and is most often diagnosed within the first year of life, with one study showing a median age of diagnosis of 5 mo.^{11,13,14,16–19} Hypoplastic trachea may also be an incidental diagnosis in asymptomatic patients that have thoracic radiographs taken later in life.

In the absence of concurrent pulmonary disease, tracheal hypoplasia is usually not associated with clinical signs.^8,10–14,17 It may exacerbate the respiratory signs associated with brachycephalic airway syndrome because of increased resistance to airflow, but tracheal hypoplasia was not associated with worse outcomes after surgical correction of brachycephalic syndrome.^{1,6,7,10,16,17,19} In disease states associated with increased production of airway secretions, the hypoplastic trachea may more easily become partially obstructed by secretions, thereby delaying or preventing resolution of pneumonia.^1,14 The possibility of a narrowed tracheal diameter should be considered when selecting endotracheal or tracheostomy tubes for brachycephalic patients. Tracheal hypoplasia has been considered a negative prognostic indicator when it occurs in association with brachycephalic airway syndrome or bronchopneumonia.^1,10,11,15

Palpation, radiography, tracheobronchoscopy, and fluoroscopy have been used to diagnose tracheal hypoplasia.^{8,10,11,13,15–20} The most commonly used radiographic method of diagnosis is the measurement of the internal tracheal diameter (TD) and the thoracic inlet diameter (TI) on a lateral thoracic radiograph, which are then expressed as a ratio (TD:TI). The benefits of this method are that it is independent of the size of the patient and phase of respiration; however, errors can occur if the patient is not properly positioned in lateral recumbancy for the radiograph.^19,20 Previously reported mean TD:TI ratios were 0.127 in bulldogs, 0.160 in non-bulldog brachycephalic breeds, and 0.204 in nonbrachycephalic breeds.¹⁹ There is little information in the literature about TD:TI in dogs with concurrent pulmonary disease, or about growth of the trachea in bulldog puppies with a diagnosis of hypoplastic trachea.

The objectives of this study were to retrospectively evaluate the TD:TI in bulldog puppies presenting with bronchopneumonia, and to reassess the ratio in the same dogs at mature body size. A population of nonbrachycephalic puppies meeting the same inclusion criteria was used as a control group for comparison.

Materials and Methods

Medical records at the authors' institution were electronically searched from January 1991 to July 2008 to retrospectively identify all puppies diagnosed with bronchopneumonia. The parameters used for the computerized search were dogs between 2 and 6 mo of age with a diagnosis of pneumonia or bronchopneumonia. From these results, all records were evaluated by the authors to determine if the criteria for bronchopneumonia and follow-up thoracic radiographs were met. For the purpose of this study, a diagnosis of pneumonia was based on the documentation of clinical signs of respiratory disease, with concurrent radiographic findings of a dense interstitial or alveolar pulmonary parenchymal pattern consistent with pneumonia. Assessments of radiographic abnormalities were made by board certified veterinary radiologists at the authors' institution. Puppies were included in the study if one or more lateral thoracic radiographs were obtained at the initial pneumonia diagnosis and another set of radiographs obtained at least 6 mo later were available for retrospective review. The study population was divided into two groups: bulldogs and a control group of nonbrachycephalic breeds. Because of the small numbers identified (n=2), non-bulldog brachycephalics were excluded from the study.

TD and TI were measured on the lateral thoracic radiographs for each dog. TI was measured from the ventral aspect of the midpoint of the first thoracic vertebra to the dorsal surface of the manubrium at its thinnest point. TD was measured as the intraluminal TD at the intersection of the trachea with the TI measurement line. The measurements were expressed as a ratio TD:TI (Figure 1).^8,10 The same measurements were repeated on the radiographs from the same dogs at the later time point. When more than one lateral thoracic radiograph was available at a given time point, the average TD:TI value for that time point was calculated and used in the analysis. All radiographs included in the study were of acceptable lateral positioning.

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The data were expressed as the median (range) and mean± standard deviation (SD) for both groups. Given the small sample size for the groups, both parametric and nonparametric statistical analyses were used throughout. Normal distribution was assessed with both the Kolmogorov-Smirnov and D'Agnostino-Pearson tests. Comparison within groups was done using a paired samples t-test and a paired, nonparametric Wilcoxon test, whereas comparison between groups was performed with an independent samples t-test and an unpaired, nonparametric Mann-Whitney test. Statistical significance was expressed as P<0.05. All statistical calculations were performed using statistical software^a.

Results

During the study, a total of 35 bulldog puppies and 134 non-bulldog (other brachycephalic and nonbrachycephalic) breed puppies between the ages of 2 and 6 mo were diagnosed with bronchopneumonia at this institution. Fifteen of these puppies met the inclusion criteria by having an available set of thoracic radiographs >6 mo later. There were six English bulldogs and nine nonbrachycephalic breeds. The nine nonbrachycephalic dogs consisted of two mixed breeds, two golden retrievers, and one each of the following breeds: soft-coated Wheaten terrier, Jack Russell terrier, miniature poodle, miniature pinscher, and a Neapolitan Mastiff.

Normal distribution of all data was confirmed with the Kolmogorov-Smirnov test. Using the D'Agnostino-Pearson test, normal distribution could only be confirmed for the nonbrachycephalic group because the bulldog group sample size (n=6) was too small to perform this test.

Median age at initial diagnosis of bronchopneumonia for the bulldog puppies was 3.13 mo (range, 2.50–3.75 mo) and 3.50 mo (range, 2.25–5.75 mo) for the nonbrachycephalic puppies, which was not statistically different (P=0.46). There was no difference between the mean age of diagnosis of bronchopneumonia for the bulldogs (3.17±0.56 mo) and the nonbrachycephalics (3.67±1.18 mo) (P=0.35). The causes of pneumonia in the bulldog puppies were confirmed bordetella infection (n=3), and suspected or confirmed aspiration (n=5). In the nonbrachycephalic puppies, the causes of pneumonia were confirmed bordetella infection (n=3), confirmed or suspected aspiration (n=5), and an unknown etiology (n=2). The time between the first set of radiographs and the follow-up radiographs ranged from 6.00 to 46.25 mo (median, 7.40 mo) for the bulldogs, and from 6.00 to 53.25 mo (median, 10.50 mo) for the nonbrachycephalic dogs, which was not statistically different (P=0.53). No difference was present when comparing the mean time to follow-up radiographs between the bulldogs (13.79±15.95 mo) and nonbrachycephalics (19.97±17.80 mo) (P=0.51). The clinical reasons for the follow-up radiographs varied. In some dogs, bronchopneumonia was still present or resolving and the radiographs were taken to evaluate the original presenting respiratory disease (bulldogs, n=3; nonbrachycephalics, n=5). In others, the second set of radiographs was obtained for evaluation of a separate respiratory problem (bulldog, n=1, rule out aspiration pneumonia; nonbrachycephalics, n=2, rule out bronchial disease and determine source of new cough), another disease process (nonbrachycephalics, n=1, Cryptococcus diagnosed on lymph node aspirate), or before anesthesia (bulldogs, n=2, check tracheal size before anesthesia; nonbrachycephalics, n=1, preoperative thoracic radiographs for lung lobectomy).

Table 1 shows the median and mean TD:TI ratios in bulldog and nonbrachycephalic puppies with bronchopneumonia, and the ratios in the same dogs at mature body size. It is important to note that the TD:TI ratio increased in all six bulldogs with mature body size. Figures 2 and 3 show representative radiographs from this study, obtained during puppyhood and mature body size from bulldogs and nonbrachycephalic breeds, which visually demonstrate the radiographic appearance of the trachea over time.

TABLE 1 Tracheal Diameter (TD) to Thoracic Inlet Distance (TI) Ratios in 15 Puppies, 2–6 Mo of Age, with Bronchopneumonia, and in the Same Dogs When They Reached Mature Body Size

P < 0.05 considered significant.

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Discussion

This study demonstrated that in six bulldogs that presented as puppies with bronchopneumonia, hypoplastic tracheas improved significantly in terms of both median and mean TD:TI ratios when the dogs grew to mature body size. In contrast, a control group of nonbrachycephalic dogs had no statistically significant change in either their median or mean TD:TI ratios between puppyhood and adulthood. This finding was clinically important because it might be assumed that tracheal hypoplasia will be a long-term negative prognostic indicator, which might prompt a decision to euthanize affected puppies. These findings suggested that although tracheal hypoplasia in bulldog puppies with pneumonia might contribute to short-term morbidity, it might not adversely affect long-term prognosis, because the TD:TI ratio might increase as the dog grows to mature body size. Although the TD:TI ratio might improve with age, tracheal hypoplasia might not completely resolve, as it could still be seen in adult dogs with concurrent brachycephalic airway disease.^1–3,5–13

The authors chose the TD:TI ratio as the method to diagnose tracheal hypoplasia because it did not require knowledge of the patient's weight and was not affected by the phase of respiration.^19,20 This method used the TI as the comparison measurement, which was less susceptible to errors than small structures, such as the rib or manubrium. When properly positioned, the measurements were not subject to errors resulting from magnification, although errors could occur if the dog was not properly positioned for a lateral radiograph.^19,20

The previously reported mean TD:TI ratio was 0.127±0.038 in bulldogs, which was less than that of non-bulldog brachycephalic breeds (0.160±0.034).¹⁹ In that report, brachycephalics in general had significantly narrower tracheas than those of the nonbrachycephalic breeds (brachycephalic mean TD:TI, 0.136±0.039) compared with nonbrahcycephalic mean TD:TI (0.204±0.031) (P=0.0001).¹⁹ These determinations were made using dogs of varying age and degree of respiratory disease. The bulldog puppies in this study had a mean TD:TI ratio less than the previously reported mean for bulldogs <1 yr old (0.07±0.01 compared with 0.130±0.043), as did the nonbrachycephalic puppies in this study compared with nonbrachycephalics of all ages (0.15±0.05 versus 0.204±0.031).¹⁹ This difference in mean TD:TI values might be attributable to the small sample size, younger dogs in the puppy group, and the presence of concurrent bronchopneumonia with resultant airway inflammation.^18,20 At adult body size, the mean TD:TI ratio for the bulldogs was higher than the previously reported mean TD:TI for bulldogs of all ages (0.15±0.02 versus 0.127±0.038).¹⁹ The mean TD:TI ratio for the nonbrachycephalic adult dogs was less than the previously reported mean for nonbrachycephalics of all ages (0.18±0.03 compared with 0.204±0.031).¹⁹ The variability in these results might be due to the small sample size in each group and differences in age distribution between the two studies.

Decreased tracheal lumen diameter was reported in animals with inflammatory tracheal disease.^15,18,20 Inflammatory exudate and/or mucus lining the trachea could make the tracheal lumen appear radiographically narrow, which could make the degree of tracheal hypoplasia appear worse than it really was. The authors included the control group of nonbrachycephalic puppies with pneumonia in an attempt to eliminate errors of over-diagnosis of tracheal hypoplasia because of airway inflammation. In the nonbrachycephalic puppies with pneumonia, TD:TI ratios were higher than those of the bulldog puppies, despite the presence of similar amounts of inflammation of the respiratory tract. The authors did not study the presence or absence of ongoing inflammatory disease in the follow-up radiographs of either the bulldogs or the nonbrachycephalics.

This study was the first to confirm a change in relative diameter of the trachea with growth in individual brachycephalic dogs. The authors found that the measured TD:TI ratio for each individual bulldog puppy improved with maturity. In the important study of Harvey and Fink, it was reported that bulldogs, non-bulldog brachycephalics, and nonbrachycephalics <1 yr of age had significantly smaller TD:TI ratios than other dogs in the same categories that were >1 yr of age.¹⁹ These data supported that finding in bulldogs, but differed from their findings in regard to the nonbrachycephalic dogs. In this study, there was no significant difference in the TD:TI of the nonbrachycephalics as they matured.

In the study of Harvey and Fink, there was no significant difference between TD:TI ratios of bulldogs with and without respiratory disease.¹⁹ In another important study of dogs of all breeds diagnosed with tracheal hypoplasia, the TD:TI ratio was not correlated with dyspnea.¹³ However, this conclusion should be interpreted with caution because only 7 of 103 dogs in that study had pulmonary parenchymal disease at the time of diagnosis of tracheal hypoplasia.¹³ By definition, all of the dogs in this study had significant respiratory disease, but because of the study design, these findings did not provide information about the short-term influence of tracheal hypoplasia on prognosis. Because the authors wished to evaluate changes in tracheal diameter over time in individual dogs, the authors excluded dogs for which follow-up radiographs were not available after they had reached mature body size, thereby introducing a possible selection bias. Some of the excluded dogs might have had mild pneumonia that resolved quickly and did not require 6 mo follow-up, or follow-up might have occurred with the primary veterinarian. Others might have had such lung severe disease that they died or were euthanized before follow-up could be obtained. Thus, the authors had to be cautious about interpreting any effect of tracheal hypoplasia on short-term prognosis based on these results.

Hypoplastic tracheas are characterized by small tracheal cartilage rings, the ends of which overlap and are covered by connective tissue, and a narrow or absent dorsal tracheal membrane (Figures 4, 5, and 6).^{1,8,10,13–16} During normal tracheal development in utero, the laryngotracheal groove is a medial ventral extension of the caudal primordial pharynx.^21,22 The developing trachea grows caudally while remaining ventral and parallel to the esophagus. The lining of the trachea is formed from the laryngotracheal endoderm (previously the foregut endoderm), whereas the cartilage, connective tissue, and muscle within the wall of the trachea are derived from mesenchymal cells.^21,22 In dogs with tracheal hypoplasia, it is possible that the adventitia surrounding the developing trachea does not properly expand as the trachea widens, which constricts tracheal diameter growth and causes overlapping of the ends of the tracheal cartilaginous rings. An alternative hypothesis involved abnormalities in embryogenesis, with a smaller than normal laryngotracheal groove, which was suggested as a possible explanation for concurrent megaesophagus and tracheal hypoplasia.¹³ In one large study describing dogs with tracheal hypoplasia, 11 of 103 dogs had concurrent megaesophagus.¹³ Only one nonbrachycephalic dog in this study had concurrent megaesophagus, making the theory of a small laryngotracheal groove less plausible based on these results.

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It was possible that the degree of overlap of the ends of the tracheal cartilage rings might decrease as the animal grew, resulting in an increase in luminal diameter. The connective tissue contributing to the overlapping ends of the tracheal cartilaginous rings might become weaker or stretch with age, allowing expansion and reduced overlap as the dog grew to mature body size. In normal dogs, the proteoglycan content of canine tracheal cartilage increases with age, whereas water content decreases.²³ Cartilage composition is uniform along the length of the trachea in both puppies and adult dogs.²³ Increased proteoglycans and lower water content leads to decreased relaxation and increased stiffness of the tracheal cartilage, which might contribute to expansion of hypoplastic tracheas as the animal matures. The lack of variability in cartilage composition throughout the length of the trachea might explain why there appeared to be uniform improvement of tracheal luminal diameter along the whole trachea.

The dorsal tracheal membrane, which contains the trachealis dorsalis muscle, is often narrowed or absent in dogs with tracheal hypoplasia. This could result from defective mesenchymal cell development. It may also be a complication of a “disuse atrophy,” which could occur when the membrane and muscle are confined within the surrounding connective tissue that causes the ends of the tracheal cartilaginous rings to be in close apposition or overlapped. Because the dorsal tracheal membrane may be absent, or if it is present, it may not be able to contract properly, alternative mechanisms for airway clearance are needed.^13–16,19 In dogs and other animals, including rabbits, the muscles between the tracheal cartilages insert on the external surface of the cartilage rings.²⁴ In rabbits, these muscles have the ability to constrict the trachea lengthwise because of their insertion between and external to the cartilaginous rings. Circumferential constriction of these muscles, combined with contraction of the trachealis dorsalis muscle, results in overall shortening of the tracheal length as well as constriction of the airway.²⁴ In dogs with tracheal hypoplasia and a narrowed or absent dorsal tracheal membrane, the constrictor function of the muscles between the tracheal rings may be the only method of altering tracheal size to aid in the clearance of airway secretions, which may also contribute to the radiographic appearance of tracheal hypoplasia.

Conclusion

Tracheal hypoplasia may coexist with brachycephalic airway syndrome. In the six bulldog puppies studied, the median and mean TD:TI ratio at the time of pneumonia diagnosis was only 0.07, which might prompt a euthanasia decision because of the apparent severity of the airway disease. However, follow-up radiographs taken at mature body size show normalization of the ratio to the reported mean for bulldogs. Therefore, the presence of severe tracheal hypoplasia in bulldog puppies with bronchopneumonia should not be considered a poor long-term prognostic factor. Prospective studies evaluating individual tracheal growth and development over time, in all breeds of dogs, as well as those with and without concurrent respiratory disease, are warranted to make definitive conclusions about the inter-relationship among TD:TI ratio, age, and pulmonary parenchymal disease.