Aspiration and severe exacerbations in COPD: a prospective study

Discussion

We hypothesised that prandial aspiration occurs in COPD contributing to severe episodes of AECOPD. Our findings establish that aspiration, measured via “gold standard” videofluoroscopy, is found in ∼20% of patients and that individuals with evidence of aspiration have an increased propensity to severe AECOPD. Further research is needed to establish whether this association is causative, to define pertinent mechanisms and to investigate practical strategies to diagnose, manage and prevent aspiration in COPD.

Eating and swallowing are important aspects of everyday living. During normal swallow, the larynx serves as a valving mechanism to provide protection from aspiration of liquid or solid material [20]. Laryngeal penetration occurs when there is entry of material into the laryngeal vestibule at or above the true vocal folds that can be cleared by supraglottic and subepiglottic compression [21, 22], expiration [23] or cough. Aspiration is defined as progression of penetrated material below the true vocal folds. Studies in healthy individuals have indicated that prandial aspiration is rare across all age groups [24–26]. However, in COPD penetration and aspiration with swallow may take place more frequently and could be of prognostic significance due to its association with pneumonia [3, 4].

Uncertainty surrounds the prevalence of prandial aspiration in stable COPD. Our previous [6] and other small studies [5] have suggested that aspiration is detectable in ∼25% of stable COPD, and two retrospective studies noted aspiration in up to 40% [7, 8]. However, several other investigations failed to detect any evidence of aspiration in this patient group [19, 27–29]. These differences are likely to reflect methodological variations including poorly characterised, small patient study groups, confounding by comorbidities (such as neurological and swallow impairment) and use of small volume or solid contrast materials and high liquid viscosity that may preclude detection of aspiration.

The current study recruited a larger cohort of patients with COPD compared to previous smaller studies [5, 6, 8, 10, 19, 27–29]. Patients had stable, verified disease at baseline, conditions that may predispose to prandial aspiration were excluded and the volume of contrast material was optimised for accurate imaging by means of videofluoroscopy. In this context our findings confirm that aspiration can be detected in up to one fifth of patients with stable COPD, confirming previous small studies [5, 6]. However, since testing was only performed on one occasion, it is possible that the recorded prevalence of 20% is an underestimation, and it will also be important to assess in further studies whether aspiration is persistently detectable.

Up to 30% of AECOPD events have no discernible cause, and other mechanisms such as aspiration may play a role [30–32]. Our previous case–control study hinted at adverse outcomes and more frequent severe AECOPD events in patients who had detectable prandial aspiration [6]. The current study therefore examined whether aspiration is associated with more frequent ED or hospital admission for AECOPD over a 12-month period. The study findings provide affirmative data with increases in overall as well as individual severe AECOPD episodes in patients with aspiration. Importantly, there was a four-fold increase in odds ratio linking aspiration with severe episodes of AECOPD in individual patients indicating that this association was not the result of a few “super-exacerbators”. These observations provide evidence that aspiration itself, or as a marker for other predisposing factors such as older age and sarcopenia, is associated with a key adverse outcome in COPD. For that reason, aspiration merits consideration in diagnostic and management approaches aiming to prevent severe AECOPD, perhaps more so in patients who have a history of frequent severe events. Future research examining aspiration and differentiating the causes of AECOPD in detail will help to ascertain the extent to which the association is causal and to explain how aspiration contributes to AECOPD.

Aspiration may cause incremental lung damage and could contribute to the excess decline in lung function noted in COPD [17, 33]. We assessed whether a greater decline in function was measurable 6 months after detection of aspiration (review after 12 months was not feasible due to logistic constraints). No differences in any parameters were noted, a not unexpected result given relatively small patient numbers, individual variations in lung function decline and the short period of study. F_ENO, as one measure of airway inflammation, was also evaluated at baseline and after 6 months with no detectable differences.

It would be useful to identify clinical or other parameters predictive of aspiration but in this respect our findings were disappointing. Although patients with aspiration had a higher age than those without aspiration, this finding is of doubtful clinical significance given a difference in mean age of only ∼2 years (table 1). Notably, aspiration was not linked to lower FEV₁ measurements or higher lung volumes (TLC) nor was there an association with respiratory rate at rest.

How and why aspiration occurs in COPD is not understood. Our data indicate that reduced laryngopharyngeal sensitivity may be important since the majority of patients had silent aspiration (Rosenbek PAS score 8 noted in >70% of individuals with aspiration) implying a degree of airway sensory impairment in this group. Absence of an effective cough reflex may thus reflect a reduced ability to sense aspirated material and to generate appropriate cough and other protective responses to clear the airway. We therefore posit that a dysfunctional “middle airway”, perhaps due to reduced timing of laryngeal vestibular closure and sensory mechanisms in COPD [5, 34], may underlie defective protection against aspiration. Finally, an interesting finding was more frequent penetration–aspiration in patients with a history of diabetes mellitus, a condition linked with sarcopenia [35], laryngeal sensory disruption [36], diabetic neuropathy and abnormal oral bacterial loads [37].

The current investigations have several caveats. First, it was a single tertiary centre study with a limited number of patients. Next, an age-matched healthy control group was not studied. Original design of the study had included this group, but the investigators were unable to obtain ethics approval due to local restrictions on radiation exposure for research purposes in healthy individuals. Moreover, there is ample evidence that aspiration is rare in healthy persons [24–26], and comparison of patients with COPD, with and without aspiration, has yielded helpful information. Third, AECOPD events were not assessed during the event itself but documented 3-monthly by patient self-report using a healthcare-based questionnaire combined with medical record confirmation that has been shown to have acceptable accuracy in this context [16]. Fourth, low-dose systemic glucocorticoids (10 mg·day⁻¹ or less) were used in ∼30% of patients. Although not recommended by current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, similar high levels of oral glucocorticoid use have been reported in other countries [38, 39]. This medication may impact muscle function leading to AECOPD, even though no association with aspiration or AECOPD was detected. Finally, other quantitative assessments such as intranasal pressure measurement for quantification of respiratory phase during swallow [6, 18], hand grip strength to assess associations with sarcopenia and a standardised instrument for frailty or age-related susceptibility may have provided additional useful information.

In conclusion, prandial aspiration can be detected in a subgroup of patients with COPD. The presence of aspiration is associated with severe AECOPD requiring ED or hospital admission. It is unclear why aspiration occurs and how this may predispose to severe episodes of acute deterioration. Future research should aim to verify causative links, improve understanding of mechanistic aspects, examine early and accurate diagnosis and design appropriate studies testing effective approaches to prevent aspiration. Finally, the findings reinforce the importance of swallow-breathing strategies [40] in COPD educational and rehabilitation programmes.