Bronchiectasis

Bronchiectasis is a condition that receives less attention in respiratory texts than conditions such as asthma and chronic obstructive airways disease. This is primarily owing to the fact that bronchiectasis represents a disease process rather than a specific entity and can commonly occur as part of a systemic disorder, as discussed below. It is defined as the abnormal dilation of proximal, medium-sized bronchi (>2 mm diameter) due to lysis of the elastic and muscular components of their walls.Reference Lode^2, Reference Murray³ This lysis is mediated by the enzymes collagenase and elastase, released from neutrophils that are chemotactically attracted to the area.Reference Schuster, Ueki and Nadel^4, Reference Sepper, Konttinen, Ding, Takagi and Sorsa⁵ The cytokines that attract the neutrophils include interleukin-8 and leukotriene-B from macrophages and mucosal cells.Reference Mikami, Llewellyn-Jones, Bayley, Hill and Stockley⁶ Sometimes, this dilation is associated with chronic bacterial infection and the consequent expectoration of large quantities of offensive sputum. The condition may however be ‘dry’, when the upper lobes of the lung are involved, as these have dependant drainage. The pathological process is usually found to be irreversible, but there are a few exceptions, such as after acute pneumonia.Reference Lander⁷ There may also be overlap with other clinical entities such as chronic bronchitis, especially when the aetiologies are common.Reference Mysliwiec and Pina⁸

Several classifications for bronchiectasis have been produced, including a morphological one by Reid, published in 1950, which is as follows.Reference Reid⁹ ‘Cylindrical bronchiectasis’ denotes consistent widening of sections of the bronchi. ‘Varicose bronchiectasis’ denotes local, cylindrical constrictions, causing an irregularity which resembles varicose veins. ‘Saccular or cystic bronchiectasis’ denotes dilation increasing towards the lung periphery, with resulting ballooning of the terminal bronchi.

These classifications are useful radiologically but have little bearing clinically or pathophysiologically. That said, bronchiectasis is essentially a radiological diagnosis, and although clinical signs such as an expectorant cough may give clues, the gold standard investigation is a high resolution computed tomography (CT) scan of the chest.Reference McGuinness and Naidich^10–Reference Remy-Jardin, Amara, Campistron, Mastora, Delannoy and Duhamel¹²

Rhinitis and rhinosinusitis

Rhinitis is defined as an inflammatory disorder of the nasal mucosa, characterised by two or more of the following symptoms: rhinorrhoea (anterior and/or posterior), blockage, and itching or sneezing.Reference Scadding and Lund¹³ Rhinitis is a term that encompasses a variety of aetiologies. Allergic rhinitis has now been reclassified by the Allergic Rhinitis and its Impact on Asthma workshop into mild or moderate/severe and intermittent or persistent. The defining features for this classification are whether symptoms occur more or less than four days a week or four weeks a year, and the presence of sleep disturbance or interruption of normal daily activities.Reference Pawankar^14–Reference Bousquet, Van Cauwenberge, Bachert, Canonica, Demoly and Durham¹⁶ The importance of rhinitis in asthmatic patients is well documented, although the two are often tackled separately by respiratory physicians and otorhinolaryngologists, respectively. Allergic rhinitis is by far the most common form of nasal mucosal inflammation, and, despite being a benign disease with no systemic manifestations, its high prevalence (20 per cent of the adult population) means that it has a significant socio-economic impact due to reduced workplace productivity.Reference Bousquet, Bullinger, Fayol, Marquis, Valentin and Burtin^1, Reference Bousquet, Van Cauwenberge and Khaltaev¹⁷ It follows that allergic rhinitis can predispose towards infective sino-nasal pathology, and it is not uncommon to find atopy in patients with chronic rhinosinusitis with or without nasal polyposis.Reference Pelikan and Pelikan-Filipek¹⁸

Chronic rhinosinusitis has its own diagnostic criteria, as decided in August 1996 by the multidisciplinary rhinosinusitis task force, on behalf of the American Academy of Otolaryngology–Head and Neck Surgery.¹⁹ The resulting article, ‘Adult rhinosinusitis defined’, was published in 1997 and endorsed by the American Academy of Otolaryngology–Head and Neck Surgery, the American Academy of Otolaryngic Allergy and the American Rhinologic Society.Reference Lanza and Kennedy^20, Reference Lund and Kennedy²¹ The main defining marker is the presence of symptoms for at least 12 weeks. Along with this, the patient should have at least two major factors present or one major factor and at least two minor factors, or nasal purulence on examination (see Table I).Reference Benninger, Ferguson, Hadley, Hamilos, Jacobs and Kennedy²²

Table I

Diagnostic factors for chronic rhinosinusitis

^*Fever in acute sinusitis alone does not constitute a strongly suggestive history for rhinosinusitis in the absence of another major nasal symptom or sign. ^†Facial pain or pressure alone does not constitute a suggestive history for rhinosinusitis in the absence of another major nasal symptom or sign.

Any rhinitis of an allergic nature involves an immunoglobulin E mediated response to inhaled allergens on the nasal mucosa. The aetiology of rhinosinusitis can be broadly divided into infective and non-infective causes, but it is infection that is most important in bronchiectasis. Staphylococcus aureus, coagulase-negative staphylococcus, and anaerobic and gram-negative bacteria are the predominant organisms in chronic rhinosinusitis, as reflected by the common prescribing habits of otorhinolaryngologists, and beneficial outcomes have been noted in controlled circumstances over short periods.Reference Fairbanks^23, Reference Subramanian, Schechtman and Hamilos²⁴ What remains uncertain is the actual pathophysiological role which bacteria play in chronic rhinosinusitis; it may be that they are present by association only. Further research will no doubt be ongoing in this area.

To date, there have been suggestions in the literature of a non-infective – or specifically, a non-bacterial – aetiology evident in chronic rhinosinusitis.Reference Statham and Seiden²⁵ The sinus mucosa inflammatory infiltrate has been shown to be similar in composition to that of asthmatic patients, with typical cells including lymphocytes, mast cells, eosinophils, fibroblasts, plasma cells and goblet cells. The evidence for an immunological mechanism is underlined by the finding of an increased number of T_H2 lymphocytes positive for interleukins 5 and 13 and interferon-γ in the sinus mucosa of patients with chronic rhinosinusitis; this is despite less than 40 per cent being atopic.Reference Shin, Ponikau, Sherris, Congdon, Frigas and Homburger²⁶ It may be that bacterial and fungal colonisation provoke this immunological response without direct pathogenesis, but it remains that histological and radiological changes are evident in the presence of both bacteria and fungi.Reference Abraham, Faddis and Chole^27, Reference Ponikau, Sherris, Kita and Kern²⁸ The demoralising reality of endoscopic sinus surgery is that a small proportion of patients return to the clinic with purulent discharge, despite their widened middle meati and beautifully opened ethmoid cavities.Reference Benninger, Ferguson, Hadley, Hamilos, Jacobs and Kennedy²²

Evidence for interaction between bronchiectasis and sino-nasal disease

Kartagener's syndrome typifies the link between chronic rhinosinusitis and bronchiectasis, with the added component of situs inversus.Reference Pedersen and Mygind²⁹ The underlying problem in this syndrome is absent or possibly severely impaired ciliary motility. This scenario can also occur without situs inversus, and in this circumstance is known as primary ciliary dyskinesia.Reference Eliasson, Mossberg, Camner and Afzelius^30, Reference Sleigh³¹ As the name suggests, it is primarily a dysfunction of cilial motility rather than a loss of their function outright. Primary ciliary dyskinesia is usually a recessive condition, but there can be genetic heterogenicity. Cilial function is vital to the effective clearing of microscopic particulate matter in the respiratory tract.Reference Eley, Yates and Goodship³² The motile cilia of the respiratory tract have a nine plus two arrangement of the microtubules and associated proteins that make up the core of the cilia, known as the axoneme (Figure 1).

Fig. 1

Cilia and flagella structure.

Within the axoneme, the microtubules in the peripheral pairs differ from one another and are known as A and B tubules. The B tubules are incomplete with respect to the A tubules, in that they contain only two rather than 13 parallel protofilaments. The A microtubules also have an inner and outer row of dynein arms. In primary ciliary dyskinesia, the motile cilia are found to contain abnormalities of the dynein arms and the radial spokes. However, they also lack a central pair of doublets, and therefore have an eight plus one configuration. Occasionally, patients may have an abnormal cilial beat frequency in the presence of a normal structural configuration. Disordered orientation of the cilia (when beating) can also occur. Thus far, three genetic defects have been discovered which affect the dynein arms of the axoneme.Reference Olbrich, Haffner, Kispert, Volkel, Volz and Sasmaz^33–Reference Bartoloni, Blouin, Pan, Gehrig, Maiti and Scamuffa³⁵

Atypical cilia have also been found in normal subjects without respiratory disease, but there is some doubt as to their validity.Reference McDowell, Barrett, Harris and Trump^36–Reference Kollberg, Mossberg, Afzelius, Philipson and Camner⁴⁰ However, a study of cilial ultrastructure and function demonstrated that patients with primary ciliary dyskinesia had a significantly greater proportion of cilial abnormalities than did normal subjects.Reference Rossman, Lee, Forrest and Newhouse⁴¹ This same study also found that the patient sub-group with allergic rhinitis had a significantly higher ciliary beat frequency than the other, non-primary ciliary dyskinesia sub-groups. Another study assessing cilial orientation found that primary ciliary dyskinesia patients had a high incidence of ciliary disorientation.Reference De Iongh and Rutland⁴²

However, the effect of abnormal cilial structure and function may not account for the entire problem. Abnormal mucus could also have a role to play in the process,Reference Eliezer, Sade, Silberberg and Nevo⁴³ as was concluded by Stanley et al. Reference Stanley, Wilson, Greenstone, Mackay and Cole⁴⁴ following their study of mucociliary clearance in patients with chronic rhinitis and concomitant chest disease. Mucociliary clearance time was prolonged in patients with both allergic and non-allergic rhinitis. Furthermore, although concomitant asthma did not significantly increase it, 57 per cent of patients with chronic rhinosinusitis and bronchiectasis had mucociliary clearance times greater than 60 minutes.Reference Stanley, Wilson, Greenstone, Mackay and Cole⁴⁴ Another study of nasal mucociliary clearance in asthmatics and bronchiectatics, using 68 subjects including controls, showed a significantly impaired clearance time in both groups. These authors stated that this was due to a combination of impaired ciliary function and mucus abnormality,Reference Awotedu, Babalola, Lawani and Hart⁴⁵ and this finding has been echoed by other studies.Reference Stanley, Wilson, Greenstone, Mackay and Cole^44, Reference Rutland and Cole^46, Reference Varpela, Laitinen, Keskinen and Korhola⁴⁷

Clinical pattern of disease

Clinically, patients with Kartagener's syndrome or primary ciliary dyskinesia generally report symptoms of rhinorrhoea and/or mucopus discharge from birth.Reference Pedersen and Mygind²⁹ Not surprisingly, more than a third of patients with this syndrome are found to have nasal polyposis, and all patients fail the saccharin clearance test.Reference Eccles, Jones, Phillips and Hilgers⁴⁸Haemophilus influenzae was the most common organism found in nasal cultures taken from the inferior turbinates in a study of Kartagener's syndrome patients.Reference Pedersen and Mygind²⁹ Otitis media with effusion is also a common manifestation in these patients, and may cause them to present with conductive deafness. Primary ciliary dyskinesia may be missed in children thought to be atopic with rhinitis and asthma, but microbiological analysis of nasal discharge will usually help to clear up any confusion.Reference Williams and Gwaltney⁴⁹ These patients can also suffer infertility, and cases have been reported in which this occurs in the absence of any respiratory disease.Reference Moryan, Guay, Kurtz and Nowak⁵⁰

A 1991 Japanese study found that 5 per cent of patients with chronic rhinosinusitis had bronchiectasis. However, conversely, the same study found that 45 per cent of patients with idiopathic bronchiectasis had chronic rhinosinusitis, thus demonstrating that the presence of lower airway disease predisposed towards a much increased risk of upper airway disease.Reference Shirahata⁵¹ This same study also reported that 70 patients with chronic rhinosinusitis had a high incidence of fibro-nodular shadowing in the lungs on a chest X-ray, compared with 70 controls. Another study of patients with primary ciliary dyskinesia showed an even greater correlation between bronchiectasis and chronic rhinosinusitis, with 79 per cent of patients demonstrating both pathologies either clinically or radiologically.Reference Mossberg, Camner and Afzelius⁵²

As mentioned above, the mucociliary (saccharin) clearance test is the investigation used to confirm the diagnosis, although sometimes further confirmation will be necessary from electron microscopy of nasal biopsies or bronchial brush biopsies.Reference Biggart, Pritchard, Wilson and Bush⁵³ Traditionally, the diagnostic feature on electron microscopy was dynein deficiency. However, more recently, this has been challenged by the introduction of ciliary function analysis following ciliogenesis, which appears to have a high specificity and sensitivity.Reference Jorissen, Willems, Van and Schueren⁵⁴ In the UK, the centres which currently have a diagnostic service performing nasal brushing for primary ciliary dyskinesia assessment are the Royal Brompton Hospital, London, the Leicester Royal Infirmary and the Southampton General Hospital. In addition, genetic counselling will often be important, as the condition is predominantly inherited as an autosomal recessive trait. These patients will also often require regular chest physiotherapy in order to ensure drainage of dependent areas of the lungs; parents of affected children are often encouraged to learn the techniques themselves.