Challenges of diagnosing and managing bronchiectasis in resource-limited settings: a case study

Bronchiectasis, once an orphan disease is now gaining renewed attention as a significant cause of morbidity and mortality. It is a morphologic term used to describe abnormal, irreversibly dilated and thick-walled bronchi, with many etiologies. The management of bronchiectasis can be challenging because its pathogenetic mechanisms is still evolving. Its diagnosis and management is particularly more demanding especially in resource-limited settings like Nigeria because of delayed diagnosis and improper management with devastating consequences, hence this case study.


Introduction
Bronchiectasis is a morphologic term used to describe abnormal, irreversibly dilated and thick-walled bronchi, with many etiologies [1].
It usually affects the proximal and medium-sized bronchi [2]. The disease was relatively common during the pre-antibiotic era [3], but with improved living conditions, immunization against many childhood respiratory infections and widespread use of antimicrobial agents, it is gradually disappearing in most parts of the highly industrialized societies [4]. The above is however, not reproducible in resourcelimited settings, where poverty and high prevalence of respiratory infections still lingers on alongside poor nutrition and inadequate immunization coverage [5]. Consequently, the disease is still encountered in our environment, but diagnosis may be delayed and management challenging [4], leading to huge social and economic loss for patients and their families as many resources are channeled towards combating the disease with undesired results in most cases [6]. Also, information about Bronchiectasis is conspicuously missing from the developing world and in particular, from sub-Saharan Africa, necessitating this report. Adebonojo et al. conducted a study in which 70 patients treated for bronchiectasis diagnosed through bronchography at the University College Hospital, Ibadan between 1975 and 1978 and found that there was equal sex prevalence with a wide range of age groups affected. The study also discovered that factors such as malnutrition and chronic anemia adversely influenced the clinical course and prognosis of the disease and emphasized that management was handicapped by inadequate facilities, lack of drugs, illiteracy, poverty, superstitious beliefs and poor environmental hygiene [7].

Patient and observation
A 43-year-old woman presented to the emergency department with cough, weight loss and progressive difficulty with breathing of 2 months. Cough was insidious in onset, productive of copious thick whitish sputum, which was not foul-smelling but worse early in the morning. There was a history of fever, but no hemoptysis, drenching night sweats or contact with persons with chronic cough. At about the same period, she developed difficulty with breathing which was gradual in onset, provoked by ordinary activities such as walking and doing house chores. Difficulty with breathing progressively worsened, and became present even at rest which made her present at the emergency department. There was associated easy fatigability and orthopnea, but no Paroxysmal Nocturnal Dyspnea. She had bilateral leg and abdominal swelling, but no swelling in other parts of the body and no change in urine volume or frequency. She also complained of unintentional weight loss. Prior to the current bout of symptoms, she has been having recurrent cough for 22

Results of other investigations are as follows.
Sputum studies microscopy, culture and sensitivity yielded growth of upper respiratory flora; AFB and GeneXpert were negative for MTB.
Blood culture yielded no growth. Fingerstick glucose was 6.6mmol/L at presentation. Basal metabolic panel was within normal limit (HCO3: Spirometry revealed obstructive pattern (Table 1). Based on the Chest CT scan findings and result of other investigations, a diagnosis of Bronchiectasis probably post-PTB or secondary to poorly treated pneumonia, with infective exacerbation, complicated by corpulmonale was made. Nebulized salbutamol was added to her current treatment regimen. After 6 days on admission, patients condition deteriorated evidenced by persistent fever, respiratory distress, confusion and hypoxia (SpO2 82%) and was considered for Intensive care unit admission, bronchoscopic sampling of the lower respiratory tract, while IV Augmentin was changed to IV Cefepim. The relatives however, objected to further treatment due to financial constraint and was subsequently discharged against medical advice. She was also advised to get multivalent pneumococcal polyvalent vaccine at the nearest primary health care center upon discharge.

Discussion
Bronchiectasis is a highly devastating illness with frequent exacerbations especially in severe disease [8]. This can place a huge burden on the health system as patients utilize many health care resources including numerous clinic visits, hospitalizations, diagnostic imaging and parenteral antibiotics [9]. In resource-limited settings like physiotherapist and adequate nursing staff as well as the surgeon [10]. It follows therefore, that availability of sufficient human resources is also key in the proper management of bronchiectasis patients. Our patient did not receive such care due to paucity of staff coupled with poor socio-economic status. Moreover, there was conspicuous lack of physiotherapy equipment such as mechanical valve devices and therapeutic vests which serve integral part of the management of patients with Bronchiectasis. These facilities are not only not easily accessible in Nigeria, but also come with high costs, making it particularly difficult for patients in our setting to benefit from such services. It becomes imperative, therefore, that the best way to cut down on the existence of bronchiectasis as a disease entity in resource-limited settings is to adopt disease prevention as the watchword. This can be achieved at three levels of prevention, vis-aviz; primary, secondary and tertiary [11]. Primary prevention involves bronchiectasis is likely a common complication of such infections [12].
Improving access of patients to essential drugs, medication adherence and regular training of health care personnel to make diagnosis and treat pneumonia appropriately, are important preventive measures.
Appropriate antituberculous therapy cannot be overemphasized as tuberculosis accounts for a significant proportion of bronchiectasis in resource-limited environments like Nigeria [12]. Secondary preventive measures to deter progression of disease in patient who have already developed bronchiectasis is early diagnosis, and this requires high index of suspicion and availability of diagnostic equipment. Plain CXR finding of "tram-lines" reflecting underlying thickened and dilated bronchi is often unreliable for diagnosis of bronchiectasis, which accounted for one of the reasons the diagnosis was delayed in this patient [12]. HRCT is the current working gold standard for diagnosing bronchiectasis, because it has a very high sensitivity and specificity.
The distribution (apical versus basal and central versus peripheral) and concomitant findings, such as nodules, cavities, and/or lymphadenopathy, that can assist in narrowing the differential diagnosis [13]. HRCT is considered expensive in Nigeria due to poverty and lack of health insurance. In addition, only a few centers are equipped with this facility making ready availability a factor impeding prompt diagnosis. However patients need to be educated on the need for early diagnosis and encouraged to do appropriate investigations to enable early detection and management. Our patient had repeated treatments for pulmonary tuberculosis and several courses of antibiotics before a definitive diagnosis with HRCT was made, at which point the disease was already advanced with ensuing complications.
Following diagnosis, treating the underlying cause of bronchiectasis can also slow or prevent its progression. However, the etiology may not be apparent in about 50% of cases despite intensive evaluation.
Furthermore, only about 15% of patients have causative factors amenable to specific treatment according to a study [14]. The etiology of bronchiectasis in the index patient is not precisely known but based on the distribution of HRCT findings and epidemiologically, a post infectious cause is highly probable. Investigations such as screening for alpha-1 antitrypsin deficiency, cystic fibrosis, humoral immune defects, Aspergillus precipitins and other autoimmune markers were not done in this patient because of cost and availability. However, our patient had no features suggestive of some of these diseases such as malabsorption, rashes, arthralgia, liver disease, recurrent sinusitis, childhood infections or gastrointestinal infections.
Research has shown three important pathogenic and interactive components in bronchiectasis, namely infection, inflammation and enzymatic components of pathogenesis. These components cause chronic and self-perpetuating destruction to the airways, leading to further deterioration in bronchiectasis [15]. In contrast to healthy nonsmokers, the airway in bronchiectasis is frequently colonized with potentially pathogenic microorganisms. The most commonly found microorganism was H. influenza (55%), followed by Pseudomonas species (26%) and Streptococcus pneumonia (12%). Other important pathogens include Moraxella catarrhalis, Aspergillus and Mycobacterium avium complex (MAC). Staphylococcus aureus relatively uncommon in non-cystic fibrosis bronchiectasis (NCFB) [16][17][18]. Studies suggest that loss of diversity, with dominance of one or a few species, is associated with worse lung function and more exacerbations. In addition, Pseudomonas aeruginosa dominance has been associated with worse lung function and more exacerbations [19]. Since progression of the disease is linked to impaired mucus clearance, airway colonization by bacteria, airway inflammation as well as airway structural damage, the therapeutic goal should be to halt or reverse these processes and break the cycle [20]. Just like other chronic lung diseases, patients with bronchiectasis should be encouraged to stop smoking and receive vaccination against influenza and pneumococcal disease. The benefits of management of treatable of identifiable causes cannot be underscored although many patients such as the index case had no readily identifiable cause [21]. The for prophylaxis with low-dose antibiotics range from daily to 1 week of each month [24]. Maintenance antibiotics has been shown to prevent detrimental infections and decrease hospitalizations in people with bronchiectasis according to a report [26].
There has been increased interest in macrolides for the treatment of NCFB because of their anti-inflammatory properties and ability to decrease mucus production. Illustrating this, Liu and colleagues showed that in patients with NCFB, 6 months of therapy with roxithromycin significantly reduced various inflammatory markers [27]. Another study demonstrated that low-dose clarithromycin decreased levels of CD4+IL-17+ cells in peripheral blood and IL-17 levels in exhaled breath condensate in patients with NCFB [28]. These studies further add to the growing evidence that macrolides may modulate inflammatory patterns in NCFB. The index patient could have benefitted from maintenance antimicrobial therapy giving the severity of her disease. The role of prophylactic inhaled antibiotics in NCFB is evolving with the aim of delivering the drug directly into airway to improve antibacterial efficacy and to reduce systemic side effects. Antibiotics that have been tried include the aminoglycosides (nebulized gentamicin/tobramycin), colistin, ciprofloxacin, and aztreonam; they have collectively demonstrated a reduction in sputum bacterial load [29]. These approach to management may not be feasible in our environment due to unavailability of these agents and high cost of procurement. Although long-term outcomes are lacking, it has been demonstrated that high doses of bromhexine coupled with antibiotics improved mucus clearance compared with placebo. They found that erdosteine when combined with physiotherapy over a 15-day period improved spirometry and sputum purulence compared with physiotherapy alone [30]. Therefore, patients need to be routinely referred for bronchiectasis. In this study, the most common procedure was segmentectomy and lobectomy [32]. If our index patient was diagnosed earlier and had localized disease, she may had benefitted from surgical treatment which could have prevented other parts of the lungs from been infected. A review by Goyal and Chang compared the value of combined inhaled corticosteroid (ICS) and long-acting ß2agonist versus high-dose ICS monotherapy and found that the combination inhaler improved subjective dyspnea and increased cough-free days compared with high-dose ICS alone [33]. However, a study on the complications of inhaler use found that there was a significantly increased risk of hemoptysis 53 days after initiation of ICS/long-acting ß2-agonist or short-acting ß2-agonist [34]. However, the routine use of bronchodilators has the added potential advantage of the stimulation of mucociliary clearance, which is associated with the use of ß-adrenergic agents. Both aerosolized ß2-agonist therapy and aerosolized anticholinergic therapy should be tried when there is Page number not for citation purposes 6 evidence of reversible airway obstruction [23]. Our index patient had obstructive pattern on spirometry but due to non-adherence to ICS and ß2-agonist, a clear improvement in symptoms cannot be ascertained. Long-term oxygen therapy (LTOT), adequate family and social support as well as effective palliative are tertiary preventive modalities to minimize physical and psychosocial complications that could arise as a result of bronchiectasis [31]. Bronchial artery embolisation and/or surgery is first-line therapy for the management of massive hemoptysis which is not uncommon in patient with bronchiectasis and a cause of mortality in some patients [24]. anti-pseudomonal compound based on the antimicrobial peptide protegrin, are welcome developments, given the complexities and drawbacks to the current treatment of bronchiectasis [21,40].

Conclusion
Bronchiectasis was initially thought to be an orphan disease, but is increasingly gaining widespread recognition due to a current rise in its incidence. It is still a source of morbidity and mortality in resourcelimited settings due to a variety of challenges in its diagnosis and management. The linchpins in the prevention and management of bronchiectasis are, the timely institution of appropriate antimicrobials to treat lung infections, high index of suspicion and prompt diagnosis and, a more aggressive management of infections in diagnosed cases to retard the progression of the disease.