Clinical history should include onset age, presenting symptoms, clinical evolution, previously diagnosed diseases, risk exposures, infertility history, non-respiratory symptoms and family history including consanguinity data (Table 1). These questions should be asked in a systematic way as patients may not value certain clinical data either because they do not significantly compromise their quality of life or because they are not aware of their relevance for the diagnosis.

The results of sputum microbiological examination as well as imaging features, in particular the location of BE (Fig. 1) are also data to be taken into consideration.

Figure 1.

Radiological characteristics and aetiology. UL, upper lobe; ML, middle lobe; LL, lower lobe.

(0.14MB).

It is common to assume/that the diagnosis is post-infectious BE when symptoms begin after a serious infection. Nevertheless, there are cases where symptoms occur only years later when another predisposing factor is established (for example, some degree of immunodeficiency). On the other hand, one should ask the patient about respiratory symptoms arising before the infectious episode as they may be related to the first exacerbation of undiagnosed BE. Therefore, despite the fact that infectious diseases are still a frequent cause of BE,3–6,10 care should be taken in establishing the diagnosis of post-infectious BE especially in the presence of upper airway symptoms, non-respiratory symptoms or other systemic diseases previously diagnosed.

If after proper investigation aetiology is still not defined, it is important to be aware of new clinical data throughout the follow up that may require a reassessment. In some systemic diseases, such as inflammatory bowel disease and rheumatoid arthritis, BE may precede its diagnosis.12,13 In other situations, there may be an evolution over the years (for instance, a patient with IgA deficiency may progress to common variable immunodeficiency).14

In certain cases, where aetiologic diagnoses are considered of exclusion, investigation has to be rigorous.

It would be impossible to address investigation of all causes of BE in this document, so only those that currently benefit from specific monitoring and treatment strategies with prognostic implications have been included.

Alpha-1-antitrypsin (AAT) is a glycoprotein, mainly produced in the liver and functions to protect the lung against proteolytic damage being a highly effective inhibitor of neutrophil elastase.

AAT deficiency (AATD) is defined by a reduced concentration of AAT in the serum and/or identification of a defective genotype. It is not a rare disease, but it is one that is underdiagnosed.15 Severe AATD affects approximately 1 in 2000 to 1 in 5000 individuals.

Protease inhibitor (PI) M is the normal allele, while the two most frequent deficient alleles are PI*S and PI*Z. The PI*Z prevalence is higher in northern and western European countries whereas the PI*S prevalence is higher in southwestern European countries. Portugal has one of the highest estimated PI*S frequency in the world (185.1/1000) with also a high PI*Z frequency (29.7/1000).16

AATD is the only established genetic risk factor for COPD, and it predisposes to severe emphysema. It may also cause liver disease and, less frequently, vasculitis and panniculitis.17

The high degree of overlap between COPD and AATD is a confounder when making a clinical diagnosis. The most common pulmonary symptoms in patients with AATD include dyspnoea, cough, sputum expectoration, wheezing and frequent exacerbations.

Distinctive and suggestive features of the emphysema associated with AATD may include:

• •

  Early onset (in the fourth and fifth decades)

• •

  Emphysema out of proportion to risk factors (e.g. tobacco smoking, occupational exposure)

• •

  Panacinar pathology

• •

  Disproportionate emphysematous involvement of the lung bases

Although these suggestive features, there are no clinical characteristics that reliably distinguish COPD from AATD.

AATD diagnosis is based in laboratory data.

Three strategies are commonly used to diagnose AATD: measurement of the serum or plasma protein level, AAT protein phenotyping of serum or plasma, and AAT genotyping. If the AAT protein level is below the normal range, further assessment with protein phenotyping or genotyping is recommended.

As AAT is an acute phase protein, serum concentrations can be used reliably for diagnostic testing only if no inflammation is present at the time the blood sample is drawn.

A new diagnostic tool, the AlphaKit QuickScreen®, directly detects the Z protein in a sample of blood. It is a screening test (a positive indicates the need for phenotyping or genotyping) that can be performed during a clinic visit with results available in 15–30min. It has considerable potential to increase the overall AATD detection rate.

The role of AATD in the aetiology of BE has been the subject of debate and contention over the years.18

An association was postulated after a number of case reports has linked severe (PI*ZZ phenotype) AATD to BE in individual or small numbers of cases. In these reports the incidence of BE in patients with AATD was remarkably similar, with a common overall estimate of about 40%.19–21

However, isolated case reports cannot provide any causal link between these two conditions. Moreover, some of these patients had other clinical conditions potentially leading to BE.22

A case-control study indicates that AAT phenotype distribution and gene frequencies are not different between patients with bronchiectasis and control subjects.22 However, this study highlights the importance of bronchiectasis associated emphysema. The authors show that bronchiectatic patients without emphysema do not have a different AAT distribution as compared with control subjects in contrast to bronchiectatic patients with emphysema. This suggests that bronchiectasis may be a consequence of emphysema in PI*Z patients rather than a primary cause.22

One small case-control study reported a possible increased frequency of the Z allele among patients with bronchiectasis and common variable immunodeficiency.23 Two other studies suggest that immune deficiency may combine with selected AATD phenotypes to elicit clinically significant bronchiectasis.10,24

Parr et al. have demonstrated that 27% of 74 AAT-deficient patients had High-Resolution Computed Tomography (HRCT) evidence of BE. That study indicated a concordance distribution of airway disease and emphysema with greater severity demonstrated in the lower lung. This concordance may reflect the influence of a field effect on a common pathogenic mechanism or may indicate that there is an interaction between the inflammatory processes that are considered to be putative in each condition. BE may be a consequence of emphysema, as previously suggested, but the reverse mechanism is equally plausible.25

The Canadian guidelines say that there is insufficient evidence in the literature to support routine targeted testing for AATD in individuals with BE.26

In a recent publication the REDAAT (Spanish registry of patients with AATD) group suggests that in patients with BE the AAT serum concentration should not be assessed by routine processes, but individualized.27

Further studies with a larger number of patients are required to confirm the relationship between AATD and BE and establish guidelines with a stronger evidence level.

In the context of the mixed results reported in the literature, the high frequency of deficient alleles in the Portuguese population, and the benefit from early detection of AATD (behaviour modification, optimized clinical management, existence of specific treatment for selected patients and genetic counselling) it was the consensus of the Working Group that testing for AATD should be undertaken in all individuals with BE.

AATD may play a role which is contributory to, and cumulative with other diseases as the aetiology of BE.

Primary ciliary dyskinesia (PCD) is a rare, heterogeneous autosomal recessive genetic disorder with an estimated incidence of 1 per 10,000–20,000 births.28 It is characterized by abnormal ciliary ultrastructure or function, with wide clinical spectrum frequently involving recurrent respiratory infection due to defective mucociliary clearance.29 Inheritance usually follows autosomal recessive pattern.30

Age at presentation range from birth to adulthood. Presenting symptoms according to age are:30–32

• •

  In the newborn period

  • ∘

    Neonatal respiratory distress or pneumonia without any obvious predisposing factors

  • ∘

    Continuous rhinorrhea from the first day of life

  • ∘

    Associated features: disorders of laterality, complex congenital heart disease, heterotaxy, hydrocephalus, cleft palate, bilateral cervical ribs, biliary atresia, esophageal abnormalities, anal atresia

• •

  In the infants and older children

  • ∘

    Chronic productive cough, recurrent upper and lower respiratory tract, BE

  • ∘

    Chronic rhinosinusitis (rarely nasal polyps)

  • ∘

    Recurrent otitis media with effusion, hearing loss

• •

  In the adults

  • ∘

    Same as for children

  • ∘

    Nasal polyposis and halitosis

  • ∘

    Ectopic pregnancy, subfertility in females; infertility in males (50%)

In practice, patients with clinical picture suggestive of PCD should be screened, and diseases with similar features (e.g. CF, immunodeficiency) excluded. Any positive screening testing requires confirmatory diagnostic testing to demonstrate abnormal structure and/or function of cilia.30 The screening test and the diagnostic test should be performed on clinically stable patients, free of acute upper or lower respiratory illness for at least 4–6 weeks before undergoing measurements (Table 2).30,32–34

A lower threshold for screening should be considered in newborn and infants or when patient has a consanguineous background.

In adults the diagnosis of PCD should be questioned in the absence of BE.28,31

In a cohort study 98% of adults and 61% of children with primary ciliary dyskinesia had BE.35

Allergic Bronchopulmonary Aspergillosis (ABPA) is a non-invasive disorder caused by hypersensitivity to a ubiquitous fungus called Aspergillus fumigatus after inhalation of its spores.36 ABPA almost always occurs in patients with asthma or CF.36 It is estimated that 2% asthmatics and 1–15% of CF patients may develop ABPA but this condition remains underdiagnosed and the mean diagnostic latency is 10 years after the onset of symptoms.37

ABPA occasionally could complicate other chronic lung diseases, namely idiopathic BE or secondary to other causes.37

There is no gender predilection and the majority of cases occur in the 3rd and 4th decade.

Most patients present with low-grade fever, weight loss, worsening wheezing, worsening dyspnoea and productive cough with expectoration of very thick mucus and sometimes well-formed brownish-black mucus plugs.37,38

ABPA clinical course may evolve into 5 different Stages: Stage I – Active ABPA; Stage II – Remission; Stage III – Recurrence or exacerbation; Stage IV – Steroid-dependent ABPA; Stage V – Fibro-cavitary disease.36

The prevalence of BE in ABPA ranges from 69 to 78% in different studies.42

CF is the most common autosomal recessive disease among caucasian populations.43,44

It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, that results in dysfunction of the apical membrane CFTR protein, which regulates chloride and sodium transport in secretory epithelial cells, leading to abnormal ion concentrations across the apical membranes of these cells.45

CF is a multissistemic disease. It is associated to a large number of mutations (>2000),46 responsible for different types of dysfunction of the CFTR protein and consequently with a wide variability of fenotipic expression.47

The term ‘CFTR-related disorders’ is used to describe a clinical entity which is also associated with CFTR dysfunction, but that does not fulfil all the diagnostic criteria for CF.48 Three main clinical entities illustrate these phenotypes:

• •

  CBAVD (congenital bilateral absence of the vas deferens)

• •

  Acute recurrent or chronic pancreatitis

• •

  Disseminated BE

Clinical features and their prevalence in CF patients include:49,50

• •

  Disseminated BE – 95% (chronic colonization with certain microorganisms such as Staphylococcus aureus and Burkholderia cepacea complex being very suggestive of this disease)

• •

  Sinus disease with panopacification of the sinuses – 90–100%

• •

  Pancreatic exocrine insufficiency, leading to malabsorption – 85%

• •

  Sweat gland salt loss – 100%

• •

  Male infertility (absent or altered vas deferens) – 99%

• •

  Meconium ileus – 20%

• •

  Distal intestinal obstruction syndrome – 20%

• •

  CF-related diabetes – 20%

• •

  CF liver disease – 20%

• •

  Nasal polyps – 10%

However, many patients demonstrate mild or atypical symptoms, with less severe pulmonary disease and pancreatic sufficiency and clinicians should remain alert to the possibility of CF even when only a few of the usual features are present.44

The clinical features of the CFTR related disorders are usually restricted to only one organ or system.

The criteria to establish the diagnosis of CF are:51

• •

  one or more of the characteristic phenotypic features or

• •

  a history of CF in a sibling or

• •

  a positive neonatal screening test result

And

• •

  an increased sweat chloride concentration (>60mmol/l) or

• •

  identification of two CF mutations or

• •

  demonstration of abnormal nasal epithelial ion transport

As CF is associated with a more rapid progression and considerably greater mortality than non-CF BE, it is important to identify these cases.18

The diagnosis of disseminated BE with CFTR dysfunction can only be admitted in the presence of at least one CFTR mutation and after rolling out other possible aetiologies including a mild form of CF, which can be extremely difficult.48

The true prevalence of BE among children with CF is unknown; however, studies have shown that 50–70% of patients have HRCT-defined bronchiectasis by 3–5 years of age.52 Once present, BE persists and progresses in approximately 75% of young children, despite receiving of the best current therapy and by adulthood the prevalence raises to approximately 95%.

Primary immunodeficiencies (PIDs) are a heterogeneous group of rare and complex diseases that include more than 230 different disorders caused by ineffective immune function resulting from different mechanisms.54 Predominantly antibody deficiencies constitute the most prevalent group of PIDs.54,55 These include the PIDs that more frequently present with BE as sequelae of recurrent chest infections3,56,57 particularly common variable immunodeficiency (CVID), specific antibodies deficiency, X-linked or autossomic recessive agammaglobulinaemia, IgA deficiency and Good syndrome.

PID recognition is crucial for early diagnosis and appropriate access to treatment, limiting infections and secondary structural damage. Considering PID is the key to diagnosis.58

The hallmark of PID is infection. Patients with antibody deficiencies present with recurrent infections, most frequently caused by encapsulated bacteria and affecting the respiratory tract. These infections, besides increased frequency, typically fail regular treatment and become chronic or evolve to severe complications.58

CVID is the most prevalent symptomatic PID in adulthood (1:50,000 inhabitants in western countries).59 Besides infections, other features may be found in CVID, including prolonged or recurrent diarrhoea and/or different expressions of autoimmunity or lymphoid proliferation.

Specific antibody deficiencies are much more rare and are frequently associated with complicated BE. In 2008, Agamohammadi et al. reported that 30% of the patients with BE classified as idiopathic presented decreased response to vaccination, allowing their aetiologic reclassification as specific antibody deficiency.60

PID diagnosis is often missed when specific antibody testing is not performed in patients with recurrent chest infections and normal levels of total serum IgG.60

Agammaglobulinaemia is a PID characterized by the arrest of B cell differentiation, leading to a considerably reduced B lymphocyte count and very low serum Ig levels. Infections usually start occurring between 3 and 6 months of age, when maternal IgG levels start to decline. Lifelong immunoglobulin replacement therapy is indicated. Early treatment with IgG is essential to reduce the infections recurrence and severity although BE may develop during follow-up in patients with adequate IgG replacement therapy.61

IgA deficiency is the most frequent PID (1:600 inhabitants in western countries), but the vast majority of patients in this group is asymptomatic.62 If IgA deficiency is diagnosed in a patient with BE, IgG subclasses quantification and specific antibody testing must be performed.60 IgA deficiency may evolve to CVID or specific antibody deficiency.

Good syndrome (timoma with immunodeficiency) is a rare cause of combined T and B cell immunodeficiency. Usually present in the 4th or 5th decade of life and clinical characteristics are increased susceptibility to bacterial infections with encapsulated microorganisms and opportunistic viral and fungal infections.63

The main features of these pathologies are mentioned in Table 3. Other causes of hypogammaglobulinemia must be excluded.

Several reports have shown that IgG replacement therapy should ensure serum IgG levels (above 1000mg/dL) in order to allow a cutback in the progression of lung deterioration and decrease of severe bacterial infections frequency.64–66

• •

  Serum immunoglobulin levels – IgG, IgA, IgM and IgE

• •

  Serum IgG subclass titres

• •

  Specific antibodies (quantification by ELISA) – total IgG and IgG2 for pneumococcal antigens and IgG1 for tetanus toxoid antigen

  • ∘

    if low titters are detected, access vaccine response after 4–6 weeks; specific antibodies should increase >4 times pre-vaccination level

• •

  Peripheral blood lymphocyte main subpopulations–including T cells (total CD3 and CD4 and CD8 subpopulations), B cells and NK cells

BE has been reported in up to 76% of patients with CVID, being more frequent in cohorts with a longer diagnosis delay. BE development in CVID has been associated with severe/recurrent respiratory tract infections and history of pneumonia,67 unregulated inflammation, lower numbers of memory B cells and CD4+ T-cell counts below 700/μl.68

A study of lung complications in 30 patients with antibody deficiencies showed that 53% had CT scans abnormalities. Main abnormality was BE (12/16 patients), which was seen more frequently (67%) on the right middle lobe.57

Infections with nontuberculous mycobacteria (NTM) are caused by a large group of mycobacterial species, with varied spectrum of pathogenicity, other than those of the Mycobacterium tuberculosis complex and Mycobacterium leprae.

NTM are ubiquitous bacilli whose main reservoirs are water and soil. In this context exposure to these organisms is constant.69

The usual classification of NTM is established with respect to time of growth in culture.70

Slow growth of the NTM (>7 days), more pathogenic, have Mycobacterium avium complex as the most frequent cause of pulmonary NTM infection.71 Fast-growing NTM (<7 days), with a less aggressive range of organisms, can produce illness with high therapeutic difficulty and worse prognosis as Mycobacterium abscessus complex.72

Pulmonary involvement is the most common disease manifestation of NTM infections (70–90% of cases). The most frequent presentation is the chronic progressive form, rarely, hypersensitivity pneumonitis (hot tub lung).73,74

The chronic clinical presentation of nontuberculous mycobacterial pulmonary disease (NTM-PD) can be separated into two relevant patterns:70

• •

  Patients with pre-existing structural changes characterized by BE and/or cavitations resulting of previous lung diseases, especially in elderly men.

• •

  Patients with multifocal nodular BE of slow evolution and without lung underlying disease in non-smoking women (often with abnormalities of the chest cage and low body mass index).

Typical presenting symptoms of NTM-PD include respiratory symptoms such as persistent cough, often purulent sputum, sometimes haemoptysis, dyspnoea and systemic symptoms with asthenia, weight loss and intermittent fever.71

BE are associated with NTM-PD as a predisposing factor to the disease, as well as a result of it, keeping a cause and effect cycle which contributes to worsening structural damage of the airways with progressive clinical deterioration.75–77

Given the relatively low virulence of the NTM, in order to produce disease, the host has usually some level of systemic or local immune deficiency.78–80

Although not yet clinically validated, ATS/IDSA proposed diagnostic criteria of NTM-PD which includes the following:81

• •

  Suggestive clinical picture and imaging findings

• •

  Exclusion of other similar diseases (fungal disease, malignancy, tuberculosis)

• •

  Identification of NTM:

  • ∘

    at least two positive culture from separate sputum samples or

  • ∘

    culture positive in at least one sample of bronchial wash/lavage or

  • ∘

    biopsy showing histopathologic features (granulomatous inflammation) and positive culture in 1 sputum sample or 1 sample LBA or 1 biopsy sample

Patients who are suspected of NTM-PD but do not meet the essential criteria should be kept under surveillance until firmly confirmation or exclusion of this diagnosis.82

Overall NTM infections have increased significantly in recent years. There is however a great variability between regions regarding the prevalence and isolated species.83,84

The incidence of tuberculosis and NTM infection is inversely proportional. In this sense there has been a substantial increase in NTM disease in areas of low incidence of tuberculosis.85

Epidemiological studies indicate the following data:86,87

• •

  USA – incidence of 5–6/100,000 year; prevalence 10–40/100,000

• •

  Canada – prevalence 14.1/100,000

• •

  Australia – incidence 3.3/100,000

• •

  Great Britain – incidence 2.9/100,000

In a recent study, NTM were found in 37% of non-cystic BE, 30% of which met the NTM disease criteria.88

The presence of BE in a patient with obstructive airways disease may result from the intersection of prevalences or a causal relationship. Pathophysiologically it is acceptable to consider a causal link but no longitudinal studies have proved this relationship yet.2

Clinically these patients have increased systemic inflammation, poorer pulmonary function, greater number and severity of exacerbations, more production and purulence of sputum, worse quality of life and worse prognosis.2,91

In COPD, BE are typically cylindrical, small and multiple, predominating in lung bases.91 In asthma, BE can affect all lobes equally.18

Diagnosis of obstructive airway diseases (asthma or COPD) with BE on high-resolution CT without evidence of other cause.

Prevalence of BE in patients with COPD is highly variable (2–74%),91,92 probably in relation with the criteria used to define BE. Several studies have confirmed a prevalence of approximately 50% in patients with moderate-severe COPD.91,93,94

The prevalence of BE in asthma is described between 17.5 and 28%.18

Diffuse panbronchiolitis (DPB) is an idiopathic inflammatory disease that mainly affects the respiratory bronchioles, causing a suppurative and progressive severe obstructive disorder. Histologically it is characterized by chronic inflammation, centralized in the respiratory bronchioles with accumulation of histiocytes, neutrophils and lymphocytes. Foamy macrophages in respiratory bronchioles wall and surrounding interalveolar septa are one feature of DPB.95

DPB is most prevalent in the Asian population but there are cases and small series described in Caucasians, Hispanics and Afro-Americans.

It is usually diagnosed in the 2nd–5th decade of life and 2/3 of patients are nonsmokers.95

The first symptom is productive cough with abundant sputum, followed by progressive exertional dyspnoea. More than 80% of patients have chronic paranasal sinusitis.

The most frequently isolated pathogen in sputum is H. influenza, while infection with P. aeruginosa is common in later stages.

The most characteristic laboratory finding is the persistent elevation of cold agglutinins.

Pulmonary function tests usually show an obstructive pattern and low values of nasal nitric oxide.95,96

Chest CT shows poorly defined centrilobular nodules, signs of air-trapping and bronchial wall dilation/thickening. Changes are scattered but more significant in the lower lobes.96

Response to macrolides is excellent.

Cases definitely established should fulfil criteria 1, 2 and 3, along with at least two of criteria 4, 5 and 6.95

• •

  Persistent cough, sputum and exertional dyspnoea

• •

  History of chronic paranasal sinusitis

• •

  Bilateral diffuse small nodular shadows on a plain chest radiography film or centrilobular micronodules on chest computed tomography images

• •

  Coarse crackles

• •

  FEV1/FVC <70% and PaO2<80mmHg

• •

  Titre of cold haemagglutinin≥64

• •

  Due to its rarity, in Caucasians diagnosis should be based on lung biopsy.

The prevalence of BE in PBD is 100% in advanced stages.96

Gastro-oesophageal reflux disease (GERD) is a pathological condition which develops when gastric reflux causes quality of life disturbing/troublesome symptoms and/or local complications.

Accordingly to the Montreal Consensus Conference,97 GERD manifestations are grouped in two big syndromes: esophageal and extraesophageal (Fig. 2):

Figure 2.

GERD manifestations.

(0.21MB).

Adapted from Montreal Consensus.

Concerning esophageal syndromes, symptomatic syndromes can be considered in an initial evaluation. They include typical GERD symptoms (retroesternal burning and acid regurgitation) and chest pain. An endoscopic evaluation with biopsy will determine if there is lesion of the esophageal mucosa – syndromes with esophageal injury (Fig. 2).

Within extraesophageal syndromes two subgroups were considered accordingly to the causal links observed: established association and proposed association (Fig. 2).

In these syndromes, the pulmonary disorders where reflux is demonstrated include cough and reflux asthma. In idiopathic pulmonar fibrosis reflux is only considered a probable association.

Other reflux/GERD associated pulmonary diseases are referred to in the literature98,99 but the causal relationship is not established with the same probability degree as to the listed above. Among them are:

• •

  Pulmonary aspiration complications (lung abscess, BE, aspiration pneumonitis)

• •

  Chronic bronchitis

• •

  COPD

• •

  Obstructive sleep apnea syndrome

The causal relationship between GERD and BE is controversial, especially in adults, but it is recognized that GERD could have a negative clinical impact on BE patients. Some studies demonstrated an association with a poorer lung function and a more extensive disease on HRCT.100

Physiopathological mechanisms that can explain GERD pulmonary manifestations are:101,102

• •

  Vagal reflex mechanisms with bronchospasm resulting of vagal stimulation secondary to esophageal acid content (reflux asthma syndrome)

• •

  Stimulation of esophageal vagus nerve endings resulting in reflex cough (reflux cough syndrome)

• •

  Microaspiration/gastric reflux to the airways (mechanism proposed mainly on reflux cough syndrome and not so much on reflux asthma syndrome). It is known that the gastric content can be acidic or gaseous.

Extraesophageal syndromes show distinctive features from esophageal syndromes with reference to antireflux therapy response and multifactorial causes being esophageal reflux only a cofactor.

Diagnostic and therapeutic approach of extraesophageal syndromes associated GERD (namely pulmonary):99,101

• •

  In patients with typical GERD symptoms a therapeutic empiric trial could be done:

  • ∘

    double dose proton pump inhibitors (PPI) 30min before breakfast and dinner for 12 weeks (ex: esomeprazole 40mg; pantoprazole 40mg; lansoprazole 30mg).

  • ∘

    if symptoms improve and the patient is well after the 12 weeks trial, extraesophageal syndrome can be attributed to GERD; PPI dose should be reduced and evolution assessed.

• •

  In patients with GERD atypical symptoms 24-h oesophageal pH-testing with impedance study should be performed. If the exam confirms the diagnosis, therapeutic trial can be done. If not, an alternative cause for pulmonary symptoms other than GERD must be considered.

In a study by Pasteur et al. considering several BE aetiological factors, GERD was identified as causative factor in 4% of patients.5

The reported GERD prevalence in the Western world ranges between 10 and 20%.103

Recently, an observational prospective study, conducted to determine the prevalence of proximal and distal gastroesophageal reflux in COPD and BE patients, showed that it was 2 times higher when compared to a control population. The prevalence of GERD in BE was 40%, of whom 42% had clinically silent reflux.104

The authors declare that no experiments were performed on humans or animals for this study.

The authors declare that no patient data appear in this article.

The authors declare that no patient data appear in this article.