Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact.

An association between inflammatory bowel disease (IBD) and airway diseases has long been described in the literature. The majority of studies have addressed the topic from the perspective of airway diseases as an extraintestinal manifestation of IBD[1-7]. However, there is growing evidence regarding an increased risk of IBD occurrence among patients with airway diseases such as asthma[8-11], chronic obstructive pulmonary disease (COPD)[12,13] and bronchiectasis[13]. There are several similarities between these conditions, ranging from the multifactorial complex etiology to the chronic remitting-relapsing disease course and the presence of low-grade systemic inflammation. It is, therefore, likely that the complex relationship between IBD and airway diseases is not merely unidirectional, and the new evidence from population-based studies supports this hypothesis.

In this paper we review the similarities between airway diseases and IBD and address the epidemiological evidence for the association, focusing on IBD occurrence in patients with airway diseases.

Airway diseases were first described in IBD patients four decades ago in the case series of Kraft et al[66]. There is an extensive literature documenting airway diseases as an extraintestinal manifestation of IBD. Approximately 6%-47% of patients develop at least one extraintestinal manifestation[67-69] during the course of IBD, but the true prevalence of lung involvement is unknown due to the presence of subclinical pulmonary injury. It is estimated that 40%-60% of IBD patients have some degree of subclinical lung involvement evidenced through alterations in pulmonary function tests and high resolution tomographic imaging (HRCT)[70-73].

The most frequently observed alterations in pulmonary function tests are decreases in forced expiratory volume in 1 s (FEV₁)[72,73] and FEV₁/forced vital capacity (FVC) ratio, in forced expiratory flow 25%-75%[72,73] as well as in the transfer coefficient for carbon monoxide (DLCO)[73]. The severity of the observed alterations in pulmonary function tests was found to be in correlation with the endoscopic and clinical activity in UC patients[73,74] and independent of the effect of smoking[73].

HRCT imaging techniques allow the detection of lung involvement in IBD patients without overt respiratory symptoms. The most common findings are an enlarged bronchial internal diameter, peribronchial wall thickening, air trapping or the identification of airways in the extreme lung periphery[6,75]. The imaging appearance of small airway involvement in UC patients, with the “tree in bud” aspect and cellular bronchiolitis, was described as indistinguishable from the imaging findings in patients with rheumatoid arthritis or in transplant recipients, indicating thus an immunological mechanism of small airway injury[75].

In IBD patients with respiratory symptoms, airway diseases are the most commonly reported respiratory condition[4,11,73,76]. Bronchiectasis was found to occur in 22% of symptomatic cases[4,5], followed by chronic bronchitis in 20% of cases[5] and suppurative airway disease without bronchiectasis[4]. Furthermore, evidence from population-based epidemiologic studies indicates an association with asthma, bronchitis and COPD. A large matched-cohort study involving more than 8000 IBD patients found asthma to be the second most common comorbidity after arthritis in both CD and UC[11]. The prevalence of bronchitis was also significantly increased in IBD patients compared to healthy controls[11]. Studies of survival and cause of death reported a significant increase in mortality due to COPD among IBD patients[77,78].

Lung involvement in IBD can also result from the effect of IBD-specific medications. The most commonly reported associations were with interstitial lung diseases, such as interstitial pneumonitis (for Mesalamine, thiopurines and biologics) or diffuse interstitial lung disease (for Methotrexate)[3], or with diseases affecting the lung parenchyma, such as eosinophilic pneumonia (for Mesalamine and biologics)[79,80], but not with airway diseases.

Despite the substantial evidence of an IBD-airway disease association and of the complex interplay between the two groups of conditions, an interest toward the possibility of IBD occurrence in patients with pre-existing airway diseases has only recently emerged. In the last decade, a handful of population-based studies have addressed the risk of developing IBD, its incidence or prevalence in patients with asthma, bronchitis, bronchiectasis and COPD (Table 1).

Four studies have reported an increased prevalence of IBD in patients with airway diseases. In the study of Bernstein et al[11], the prevalence of CD and UC among patients with asthma and bronchitis was significantly increased compared to the prevalence in the general population of Manitoba, Canada. A four-fold increase in IBD prevalence was observed in a cohort of patients with airway diseases in the United Kingdom. The prevalence of UC was significantly increased in all types of airway disease investigated; CD prevalence was increased in patients with COPD and bronchiectasis[13]. A study of COPD patients and their first degree relatives identified from the Swedish Multigeneration Register showed an increased prevalence of both CD and UC among the patients and their siblings compared to IBD prevalence in controls[12]. Younger age at COPD diagnosis was found to be associated with a higher prevalence of UC. A case-control study of Finnish children with IBD showed that the risk of developing CD was significantly higher in children with asthma and with both asthma and cow milk allergy than in healthy controls[9].

Unfortunately, prevalence studies are informative only from the point of view of disease coexistence, and cannot provide an insight into the temporal sequence of developing these conditions. Two population-based studies assessed IBD occurrence during the course of airway diseases, one in asthmatic patients only and the other in asthma and COPD.

A study of Swedish inpatients discharged with a diagnosis of asthma showed an increased incidence of CD and UC hospitalizations during the follow up period[8]. To ensure incident IBD cases were captured, all subjects in which the diagnosis of CD and UC preceded that of asthma were excluded from the analyses. The standardized incidence rates for CD were significantly increased in all age groups, while the incidence increase of UC was only significant in subjects diagnosed with asthma after the age of 20 years.

More recently, a large retrospective cohort study of Québec patients with asthma and COPD showed a significantly increased incidence of both CD and UC in COPD patients and an increased incidence of CD in asthmatic patients compared to the IBD incidence in the general population[10]. Similar to the results of Hemminki et al[8], in asthmatic patients the incidence of CD was significantly increased in all age groups; the incidence of UC, although not significantly increased when all age groups were considered, was significantly increased in patients diagnosed with asthma after the age of 10 years. In COPD patients, the incidences of both CD and UC were significantly increased compared to the general population for all age groups. A follow up study of the same COPD cohort revealed that new onset IBD was associated with an increased risk of all-cause mortality as well as from respiratory and digestive causes[81].

The existing evidence of IBD occurrence in patients with airway diseases is supported by population based studies. In clinical settings, the true prevalence of IBD or of digestive symptoms indicative of IBD is still unknown. If clinical studies confirm the association, it would be of importance to assess whether exacerbations in airway diseases are impacted by IBD disease activity.

Inversely, in IBD patients with lung manifestations, further assessment of prevalence of subclinical airway injuries is warranted, as recent evidence suggests it is much higher than previously expected. Such an assessment could shed more light into the temporal sequence of IBD-airway disease development.

There is a complex inter-relation between IBD and airway diseases and new evidence suggests that not only can airway diseases occur as an extraintestinal manifestation of IBD, but that IBD, in turn, can have a high occurrence in patients with airway diseases. This occurrence seems to also impact on key outcomes, such as mortality in COPD patients. While the importance of airway involvement as extraintestinal manifestation of IBD is amplified by the evidence of an increased prevalence of subclinical airway injuries, the impact of IBD occurrence in patients with airway diseases raises a substantially greater public health concern due to the worldwide high prevalence of airway diseases. Early detection of IBD may improve the treatment management and prognosis of airway disease patients.

We thank librarian Tara Landry from the Montreal General Hospital branch of MUHC Libraries for assistance with the literature search.