Abstract
Feline lower airway disease (FLAD) is a chronic respiratory disease of which there is a lack of information on functional assessment in current veterinary medicine. The purposes of this study were to investigate expiratory pattern and evaluate the diagnostic utility of functional parameters in cats with FLAD. Thirty-three client-owned cats (23 FLAD cats and 10 control cats) were studied. Under quiet tidal breathing, pseudo-tidal breathing flow-volume loop (pTBFVL) was obtained from a barometric whole body plethysmography (BWBP) device. There were significant differences in the shapes of expiratory, but not inspiratory, curves between FLAD and control cats. The incidence of the presence of concave expiratory curve indicating lower airway obstruction was 74% in FLAD cats. To assess the diagnostic utility of pTBFVL indices in cats with FLAD, area under the receiver–operator curve was 0.86 for PEF/EF50 (peak expiratory flow divided by expiratory flow at end expiratory volume plus 50% tidal volume); a cuff-off value of PEF/EF50 >1.51 distinguished normal from FLAD (73.9% sensitivity, 100% specificity). There were no significant differences in traditionally measured BWBP parameters (ie, enhanced pause) between cats with and without FLAD in the present study. In conclusion, underlying change on expiratory flow pattern during natural tidal breathing existed in FLAD cats, and selected pTBFVL indices were useful in discriminating FLAD from normal cats. Tidal breathing pattern depicted by pseudoflow–pseudovolume loops from a BWBP system could be a non-invasive tool for functional assessment in client-owned cats.
Introduction
Feline lower airway disease (FLAD) is associated with the clinical conditions of recurrent chronic cough, wheeze and episodic respiratory distress. Various terms for the disease, such as ‘feline bronchial disease’, ‘feline asthma’, ‘feline chronic bronchitis’, ‘chronic bronchial disease’, ‘bronchopulmonary disease’ and ‘chronic inflammatory lower airway disease’ have been used in the veterinary literature,1–5 which implies the difficulties in establishing subsequent classifications without functional aspects of evaluation. Inflammation is believed to be the clinicopathological feature of the disease, and it was proposed to discriminate feline asthma from chronic bronchitis based on an eosinophilic or neutrophilic inflammation;3,5 however, the role of a mixed inflammation is questionable under this classification. Besides, there are still controversies regarding interpretation of varying results or techniques used for the analysis of bronchoalveolar lavage (BAL) fluid.5,6 In addition, although it was demonstrated that persistent and subclinical lower airway inflammation during high-dose steroidal treatment could be common, repeated BAL fluid collection for guiding treatment adjustment in client-owned cats is unrealistic owing to the added risk and cost. 7 Therefore, other simple and less invasive tools for either aiding classification or monitoring response to treatment are warranted.5,7
Respiratory or pulmonary function testing (RFT or PFT) is a routinely performed objective assessment in human respiratory medicine. For most chronic respiratory diseases in humans, forced expiratory flow-volume loop (FEFVL) parameters from forced maneuver are important indicators for classification of severity, the assessment of surgical risks, monitoring of disease progression and evaluation of therapeutics. Nevertheless, cats are unable to be cooperative or to exert maximal effort in the conscious state. Direct measurement of lung compliance and resistance can provide important information on ventilatory mechanics, and has been applied to either research cats or clinical feline patients;2,8,9 nevertheless, the requirement on anaesthesia or intubation is not acceptable for many pet owners owing to increased risk for respiratory patients. Non-invasive RFT, which can be performed on conscious cats, is of considerable importance.
The tidal breathing flow-volume loop (TBFVL), initially developed for use in human infants, may be applied to healthy cats and cats with bronchitis. 1 The TBFVL evaluates airflow patterns recorded with a pneumotachograph that has a differential pressure transducer. 9 In one study in cats, TBFVL was able to detect changes during tidal breathing in FLAD. 1 Nevertheless, the requirement of a tight-fitting facemask with this method means that it cannot be easily applied to many feline patients. On the contrary, barometric whole body plethysmography (BWBP) is well tolerated in cats by keeping them unrestrained in a box during recording. Signals obtained by BWBP are generated by the combination of nasal airflow and thoracic movement, and differ from flow signals produced with a facemask and pneumotachograph.9,10 Although BWBP is not a direct assessment of lung mechanics, its use for acquiring respiratory parameters and evaluating airway reactivity (AR) in cats has been validated in previous studies.3,11 –21
On both FEFVL in human adults and TBFVL in human infants, the scooped-out appearance or concave shape of the expiratory curve could be a physiological feature of lower airway obstructive disease.22,23 The incidence of this expiratory pattern under tidal breathing in FLAD cats is unknown as TBFVL recording with a facemask is not easily performed. To date and to our knowledge there are no previous studies that used non-restrained BWBP equipment to evaluate the pseudo-TBFVL (pTBFVL) in cats. The purposes of this study were to investigate pseudoflow–pseudovolume loops obtained by a BWBP device, evaluate the occurrence of concave shape of expiratory flow pattern and assess the diagnostic utility of pTBFVL indices in cats with FLAD.
Materials and methods
Animals
Cats referred for chronic coughing (intermittent; without signs between episodes) were eligible for the study. Clinical diagnosis of FLAD was assigned in this study according to the following findings: (i) a history of chronic (>2 months) coughing; (ii) episodes of repeated, but spontaneous recovery of, coughing or respiratory distress (evidence of reversibility); (iii) radiographic evidence of bronchial and/or interstitial lung pattern; (iv) abnormal thoracic auscultation (crackles or wheeze), inflammation on BAL fluid or positive response to steroidal treatment (a historical finding or a treatment received after functional assessment); (v) no clinical signs suggestive of upper airway infection; (vi) lack of pleural space disease or congestive heart failure (pneumothorax, pleural effusion, pulmonary oedema or enlarged left atrium) based on radiographic and/or ultrasonographical findings; (vii) no suspicion of pneumonia or infectious aetiology (elevated body temperature, leukocytosis, alveolar infiltration on chest radiograph, or other systemic signs). The exclusion criteria were significant upper airway obstruction with excessive inspiratory effort; the use of medication that could influence respiratory function 1 month before enrolment; and the presence of life-threatening conditions (eg, persistent dyspnoea, fever, hypothermia or other severe systemic signs). Cats without any respiratory signs, history of bronchopulmonary disease or exposure to cigarette smoke were used as controls. Thirty-three client-owned cats were enrolled in the study, including 23 FLAD cats (15 domestic shorthairs, six Persians, one Siamese and one American shorthair) and 10 control cats (eight domestic shorthairs, one Himalayan and one American shorthair) (Table 1).
Age, body weight (BW) and body condition score (BCS) in cats with feline lower airway disease (FLAD) (n = 23) and control cats (n = 10)
Functional assessment
The functional assessment was studied before giving any treatment. Data acquisition was performed by using a BWBP system (Buxco Electronics), while the system calibration and recording method were performed as previously described.11,12,20 Traditional BWBP parameters and pTBFVLs recording were acquired at the same time. Traditional BWBP parameters used in previous studies were obtained using BioSystem XA 2.11.0 software (Buxco Electronics), including respiratory rate (RR [cycles/min]), tidal volume (TV [ml]), tidal volume per kg body weight (TV/BW [ml/kg]), minute volume (MV [ml]), minute volume per kg BW (MV/BW [ml/kg]), inspiratory and expiratory time (Ti and Te [s]), peak inspiratory and expiratory flow (PIF and PEF [ml/s]), peak inspiratory and expiratory flow per kg BW (PIF/BW and PEF/BW [ml/s/kg]), relaxation time (RT [s]; the time point when 65% of tidal volume is expired), end inspiratory and expiratory pause (EIP and EEP [ms]), pause (PAU [unitless]; [Te – RT]/RT), and enhanced pause (Penh [unitless]; [PEF/PIF] × PAU). Furthermore, the box flow signals (pseudoflows) were manually set up to be continuously integrated into time to generate results that were in proportion to the estimated volume (pseudovolumes) and displayed on the x-coordinate of an X–Y diagram. While the flow signals were plotted on the y-coordinate concurrently, loops consisted of pseudoflows and pseudovolumes on this X–Y diagram were recorded as pTBFVLs and stored in graphic form. The analysis of pTBFVL was modified from previous TBFVL studies.1,24 The loops were inspected for qualitative features, and pTBFVL indices were used for delineating the overall loop shape. For each cat, 5–10 representative pTBFVLs were selected for analysis if a period of stable BWBP signals, grossly consistent loop morphology and lack of artefacts (movement, purring or vocalisation) could be achieved. Conventionally, expiration was plotted on the positive part of the graph, and inspiration was plotted on the negative part. The points that represented PEF, PIF, and expiratory or inspiratory flow at end tidal volume plus 75, 50 and 25% tidal volume (EF75, IF75, EF50, IF50, EF25, IF25) on a loop were manually measured and the ratios were calculated graphically (Figure 1). The pTBFVL indices used in the present study for delineating the overall loop shape included PEF/PIF, PEF/EF50, PEF/EF25, EF75/EF50, EF75/EF25, EF50/EF25, PIF/IF50, PIF/IF25, IF75/IF50, IF75/IF25, IF50/IF25, EF75/IF75, EF50/IF50 and EF25/IF25. The final results of each index were determined from 5 to 10 representative loops of each cat and were reported as the mean value (± SD) for each one.

Illustration of a pseudo-tidal breathing flow-volume loop in this study. The box flow is shown as the y-coordinate and the corresponding pseudovolume as the x-coordinate. The point representing the peak expiratory (PEF) or inspiratory flow (PIF) is identified as the highest or lowest point on the expiratory or inspiratory curve. By quartering the width of the loop along the zero-flow x-axis, the points representing expiratory or inspiratory flow at end-tidal volume plus 75, 50 and 25% tidal volume (EF75, IF75, EF50, IF50, EF25, IF25) on the loop are recognised. The vertical distance from the zero-flow x-axis to the corresponding point on the loop represents the value of the corresponding flow. The loop index (eg, PEF/EF50) of flow A (PEF) to flow B (EF50) is calculated by dividing the vertical distance from the zero-flow x-axis to A (PEF) by the vertical distance from the zero-flow x-axis to B (EF50). (The values of the x-coordinates are correlated to the relative variation of pseudovolume, but the absolute values representing the corresponding volumes are not available from the software here, so the scale of the x-axis is not shown)
The raw data recordings of six cats were used to replicate the pTBFVL acquisition for evaluating the reliability of pTBFVL selection and indices calculation. The originally digitised data stored in the system from each cat were replayed six times on different days, and 5–10 representative loops were selected on each replay. The measurement and calculation of pTBFVL indices from loops obtained each time were processed, respectively, and recorded as six repeated results for each of the six cats.
Statistical analysis
Descriptive statistics were used to present the data. The reliability of pTBFVL acquisition with replicated loops selection and indices measurements was estimated by intraclass correlation coefficient (ICC). An ICC value <0.40 indicates poor test–retest reliability; value ≥0.40 and <0.75 indicates fair-to-good test–retest reliability; value ≥0.75 indicates excellent test–retest reliability. 25 Intra-individual coefficient of variation (CV) for each cat’s loop indices was calculated to estimate the reproducibility of pTBFVL analysis. Mean and SD were calculated for all pTBFVL indices and BWBP parameters, and the non-parametric Mann–Whitney test was used to compare the differences between FLAD and control cats. Receiver operating characteristic curves (ROC) were computed for pTBFVL indices to evaluate the sensitivity and specificity of pTBFVL indices as measure for FLAD. Radiographic score (0–10) and cumulative clinical score (coughing frequency 1–5; dyspnoea 0–3; thoracic auscultation 0–2; general condition 0–2) modified from a previous study 21 were used in FLAD cats to analyse Spearman’s rho correlation between functional evaluation and clinical data. Statistical software (SPSS Statistics 19.0.0; IBM) was used for all analyses, and the level of significance was set at P <0.05.
Results
The shape of pTBFVL in the control cats (defined as type I, Figure 2a) was similar to that of TBFVL seen in healthy cats, dogs and human infants,1,23,24 with roughly ellipsoid-to-round conformation. In FLAD cats, two morphologic patterns of pTBFVL were identified. Seventy-four percent (17/23) of FLAD cats showed a loop with a concave shape of expiratory flow pattern (defined as type II, Figure 2b), whereas the other 26% had a loop with flattened shape in the expiratory curve (defined as type III, Figure 2c).

Examples of pseudo-tidal breathing flow-volume loops obtained from a control cat (a) and two FLAD cats (b,c). (a) The peak expiratory flow of type I loop occurred in early expiration, and the flow was gradually decreased to the end of expiration; the inspiratory limb was roughly ellipsoid-to-convex in shape. Inspiratory and expiratory parts of the loop were of similar size. (b) Type II loop had a concave shape of expiratory limb. (c) The characteristics of type III loop included relatively lower expiratory flow rate, flattened shape in expiratory limb and disproportionally smaller area under expiratory curve compared with inspiratory part. The shape of inspiratory limbs in type II and type III was basically similar to that described in type I
There were no statistically significant differences in the shapes of inspiratory curve between FLAD and control cats. In contrast to the inspiratory curve, pTBFVL indices for delineating expiratory flow pattern were significantly different between FLAD and control cats, including PEF/EF50 (P = 0.001), PEF/EF25 (P = 0.004), EF75/EF50 (P = 0.011), EF75/EF25 (P = 0.014), EF50/IF50 (P = 0.011) and EF25/IF25 (P = 0.009) (Table 2).
Mean ± SD (median) for pseudo-tidal breathing flow-volume loop (pTBFVL) indices in cats with feline lower airway disease (FLAD) (n = 23) and control cats (n = 10)
Significant difference between FLAD and control cats, P <0.01
Significant difference between FLAD and control cats, P <0.05
PEF = peak expiratory flow; PIF = peak inspiratory flow; EF75, EF50 and EF25 = expiratory flow at end-tidal volume plus 75, 50 and 25% tidal volume; IF75, IF50 and IF25 = inspiratory flow at end-tidal volume plus 75, 50 and 25% tidal volume
The discrimination power of selected pTBFVL indices between FLAD and control cats was investigated by using the ROC analysis. The area under the ROC curve was 0.86 (95% confidence interval [CI]: 0.73–0.99) for PEF/EF50, 0.82 (95% CI: 0.68–0.96) for PEF/EF25, 0.85 (95% CI: 0.66– 1.0) for EF75/EF50 and 0.84 (95% CI: 0.65–1.0) for EF75/EF25. The value of PEF/EF50 with a cut-off level of 1.51 provides 73.9% sensitivity and 100.0% specificity as a measure of detecting abnormal expiratory flow pattern of FLAD.
The results of traditional BWBP parameters are listed in Table 3. No significant differences were found between FLAD and control cats (P >0.05).
Mean ± SD (median) for barometric whole body plethysmography (BWBP) parameters in cats with feline lower airway disease (FLAD) (n = 23) and control cats (n = 10)
RR = respiratory rate; TV = tidal volume; BW = body weight; MV = minute volume; Ti = inspiratory time; Te = expiratory time; PIF = peak inspiratory flow; PEF = peak expiratory flow; RT = relaxation time (the time point when 65% of tidal volume is expired); EIP = end inspiratory pause; EEP = end expiratory pause; PAU = pause, a unitless parameter ([Te – RT]/RT); Penh = enhanced pause, a unitless parameter ([PEF/PIF] × PAU)
Replicated acquisition and calculation of all pTBFVL indices showed ICCs of single measure >0.4 (median, 0.73; range 0.46–0.89), indicating fair-to-good test–retest reliability. 25 The mean of intra-individual CVs in the current study ranged from 7.86% (PIF/IF50) to 22.27% (EF25/IF25) in FLAD cats, while 6.02% (PIF/IF50) to 23.39% (EF25/IF25) was the range in control cats.
In 23 FLAD cats, the duration of cough history (since first noted) was 27 ± 24 months (5–120 months), and the observed coughing frequency was from several times daily to less than a month. A 10-point radiographic score (1.8 ± 1.0; range 1–4) and a 12-point cumulative clinical score (5.5 ± 2.2; range 2–9) were available in 23 and 20 FLAD cats, respectively. No correlation was found between the presence of a concave expiratory curve and duration of cough history, radiographic or cumulative clinical score.
All cats in the present study could tolerate being placed in the BWBP chamber after an acclimatisation period. The time required to obtain data from each cat (including acclimatisation and data recording period in the box) was about 10–15 mins in most cases.
Discussion
The present study shows that expiratory flow pattern depicted by pseudoflow–pseudovolume loops from BWBP system can reveal the differences between cats with and without FLAD. In FLAD cats, a high incidence (74%) of concave-shaped expiratory flow pattern was found under tidal breathing. The indices of pTBFVL could be discriminative for the presence of FLAD. To our knowledge, this is the first study to acquire pseudoflow–pseudovolume loops from BWBP equipment for functional assessment in client-owned cats.
During a maximal forced expiration in an individual with obstructive airway disease, thickening of the walls of the airways and excessive secretions in the lumen can increase the flow resistance, resulting in the expiration typically beginning and ending at abnormally high lung volumes with limited flow rate. The dynamic compression of airways is reflected by the presence of a concave-shaped expiratory curve on FEFVL. 26 Although not as sensitive as FEFVL, some studies suggest a similarly useful role of TBFVL in non-cooperative patients, such as infants and young children with reactive airway disease or chronic lung disease.22,23,27 Under quiet tidal breathing, the concave shape of the expiratory curve representing the flow limitation in small airway obstruction after peak expiratory flow could also be present in a certain percentage of pediatric patients.23,27 In the current study, about three-quarters of FLAD cats showed this concave-shaped expiratory curve. The differences in expiratory flow pattern between FLAD cats and control cats could be revealed by pTBFVL indices that delineate the shape of the expiratory curve, including PEF/EF50, PEF/EF25, EF75/EF50, EF75/EF25, EF50/IF50, and EF25/IF25. With the use of PEF/EF50 as an indicator for the concave expiratory pattern, a cuff-off value of >1.51 could help discriminate cats with FLAD. The present findings provide a method of quantitative functional assessment in cats with FLAD.
In contrast to our findings, TBFVL analysis of seven cats with chronic bronchial disease did not detect concavity of the expiratory curve. 1 The loop found in those seven cats was similar to the type III loop in our study, which was shown in only a quarter of 23 FLAD cats in the current study. The difference may be due to the different equipment used in the two studies or relatively low numbers of diseased cats in the previous study. Furthermore, the respiratory strategies could be different for conscious cats, with the placement of a tight-fitting facemask in the previous study. By use of the non-restrained chamber of the BWBP system in the present study, the breathing pattern of the cats could be acquired in a less stressful and more natural condition.
The flattened expiratory curve of type III pTBFVL loop may represent one of the patterns of lower airway obstruction. This flow limitation pattern was found both on healthy neonates and infants with chronic lung disease, without significant difference between the patient groups. 23 However, in one study on human infants, it was found this type of TBFVL pattern was associated with fixed or dynamic obstruction between the glottis and the main bronchi detected by endoscopy. 27 Without endoscopic examination in neither the previous 1 nor the present study, it cannot be concluded if there were such structural problems with those cats. Further investigations are warranted in feline patients with an inconclusive functional study result.
Clinical severity assessed by radiographic and cumulative clinical scores was not correlated with the presence of concavity or PEF/EF50. It was possible that the scoring system used in this study was not enough to reflex the severity of FLAD. Besides, some FLAD cats with a severe form (eg, persistent dyspnoea) or atypical presentation (eg, alveolar infiltration on radiograph) were excluded from this study. However, the present findings may also indicate that PEF/EF50 is useful more as a diagnostic, rather than a severity, index in functional assessment of FLAD.
The traditional BWBP parameters were not significantly different between cats with and without FLAD in our study. Previous studies showed that Penh may correlate to airway limitation and lower airway disease, but there was controversy about the reliability of Penh as an indicator for AR.11,12,15,28,29 Other studies reported that all BWBP parameters at baseline measurements were normal in healthy, experimentally sensitised or bronchitis cats before allergen challenge or bronchoprovocation test.13,14 The present results suggest that including pTBFVL indices as part of baseline measurements may help to recognise the differences in breathing patterns during initial screening and reveal mechanical properties in addition to AR.
For the loop analysis, the pTBFVL indices were comparable to those previously reported in TBFVL evaluation.1,24,30 –32 However, only ratio forms of parameters were chosen as pTBFVL indices to offset the deviation caused by temperature, humidity and equipment-related effects associated with the BWBP system 20 on both inspiration and expiration. In comparison with the reported CV values of TBFVL indices in bronchitic and healthy cats (6.6% for IF25/IF12.5 to 28.4% for EF12.5/IF12.5 vs 5.6% for IF25/IF12.5 to 21.9% for EF12.5/IF12.5), 1 the range of variations in the previous and the present study are quite similar. In a previous study of dogs, the mean CV for TBFVL indices of each dog ranged from 7% (PIF/IF50) to 18% (EF25/IF25), which is consistent with the findings in our cats. 24
The present study has some limitations. Firstly, potential pitfalls may exist because the breathing pattern generated by pseudoflows and pseudovolumes of BWBP system can be influenced by factors other than airflows, such as artefacts that affect volume changes in the chamber. The longer time available to obtain data from cats with BWBP than the facemask method may also increase variation of respiratory performance. It should be borne in mind that the present method was an indirect estimate of respiratory mechanics. Secondly, caution must be taken when applying the present method to brachycephalic cats or cats with concurrent upper airway obstruction, which could induce changes in loops characteristics.
Conclusions
Functional assessment for identifying and quantifying tidal breathing was performed easily and non-invasively by pTBFVL measurements from a BWBP system in clinical feline patients. The concave shape of the expiratory flow pattern, indicating lower airway obstruction, was shown in three-quarters of FLAD cats, and selected pTBFVL indices were useful in discriminating FLAD in cats. No significant differences were found in traditionally reported BWBP parameters (ie, Penh at baseline) between cats with and without FLAD in the present study. Analysing pseudoflow–pseudovolume loops could provide additional diagnostic information in FLAD.
Footnotes
Funding
This research received no specific grant from any funding agency in the public, commercial, or non-for-profit sectors.
Conflict of interest
The authors do not have any potential conflicts of interest to declare.
Part of this study was presented in the format of poster presentations at the 29th VCRS Symposium, 3–5 November 2011, Vienna, Austria
