A Dissertation On
“COMPARISION OF SEVERITY OF NON-CYSTIC FIBROSIS BRONCHIETASIS PATIENTS BY THE TWO PROGNOSTIC
SCORES- FACED AND BSI AND EXACERBATION FREQUENCY OVER ONE YEAR FOLLOW UP”
Dissertation submitted to
The Tamil Nadu Dr. M.G.R. Medical University in partial fulfilment of the requirements for the degree of
DOCTOR OF MEDICINE (M.D) IN
TUBERCULOSIS AND RESPIRATORY DISEASES BRANCH – XVII
INSTITUTE OF THORACIC MEDICINE,
MADRAS MEDICAL COLLEGE &RAJIV GANDHI GOVERNMENT GENERAL HOSPITAL
THE TAMIL NADU DR.M.G.R. MEDICAL UNIVERSITY CHENNAI – 600032. TAMIL NADU, INDIA
MAY-2020
BONAFIDE CERTIFICATE
This is to certify that the dissertation titled “COMPARISION OF SEVERITY OF NON-CYSTIC FIBROSIS BRONCHIETASIS PATIENTS BY THE TWO PROGNOSTIC SCORES- FACED AND BSI AND EXACERBATION FREQUENCY OVER ONE YEAR FOLLOW UP” is the bonafide work done by Dr. P.SARAVANAKUMAR during his M.D (Tuberculosis and Respiratory Diseases) course in the academic years 2017-2020, at the Institute of Thoracic Medicine and Rajiv Gandhi Government General Hospital – Madras Medical College, Chennai. This work has not previously formed the basis for the award of any degree.
Prof. Dr. A.MAHILMARAN M.D., D.T.C.D Director, Institute of Thoracic Medicine,
Professor and Head, Department of Thoracic Medicine,
Rajiv Gandhi Government General Hospital and Madras Medical College, Chennai.
Prof. Dr.R.JAYANTHI M.D.,FRCP(Glasg), The Dean,
Rajiv Gandhi Government General Hospital and Madras Medical College Chennai.
DECLARATION BY THE GUIDE
This is to certify that the dissertation titled “COMPARISION OF SEVERITY OF NON-CYSTIC FIBROSIS BRONCHIETASIS PATIENTS BY THE TWO PROGNOSTIC SCORES- FACED AND BSI AND EXACERBATION FREQUENCY OVER ONE YEAR FOLLOW UP” is the bonafide work done by Dr. P.SARAVANAKUMAR during his M.D (Tuberculosis and Respiratory Diseases ) course in the academic years 2017-2020, at the Institute of Thoracic Medicine and Rajiv Gandhi Government General Hospital – Madras Medical College, Chennai, under my guidance.
Signature of the Guide,
Name and Designation of the Guide:
Prof. Dr.A.MAHILMARAN.,M.D., D.T.C.D., Director,
Institute of Thoracic Medicine,
Professor and Head, Department of Thoracic Medicine, Rajiv Gandhi Government General Hospital and
Madras Medical College, Chennai.
DECLARATION BY THE SCHOLAR
I hereby declare that the dissertation titled “COMPARISION OF SEVERITY OF NON-CYSTIC FIBROSIS BRONCHIETASIS PATIENTS BY THE TWO PROGNOSTIC SCORES- FACED AND BSI AND EXACERBATION FREQUENCY OVER ONE YEAR FOLLOW UP” submitted for the degree of Doctor of Medicine (M.D) in Tuberculosis and Respiratory Diseases, Branch XVII is my original work and the dissertation has not formed the basis for the award of any degree, diploma, associate ship, fellowship or other similar titles.
Place : Chennai DR.P.SARAVANAKUMAR
Date : Signature of the scholar
ACKNOWLEDGEMENT
My sincere thanks to Prof. Dr. R. JAYANTHI M.D.,FRCP (Glasg), The Dean, Rajiv Gandhi Government General Hospital and Madras Medical College for allowing me to do this dissertation and utilize the Institutional facilities.
I am greatly indebted & whole heartedly convey my gratitude to The Director, Institute of Thoracic Medicine., Professor and Head, Department of Thoracic Medicine, Rajiv Gandhi Government General Hospital and Madras Medical College Prof. Dr. A. Mahilmaran, M.D., D.T.C.D., for his valuable guidance, advice and encouragement throughout the study.
I sincerely thank Prof. Dr. O. R. Krishnarajasekhar, M.D., D.T.C.D., Professor, Department of Thoracic Medicine, Rajiv Gandhi Government General Hospital and Madras Medical College, for sparing his precious time in guiding my dissertation writing and reviewing it.
I sincerely thank Prof. Dr. Sundararajaperumal M.D., DCH., Professor, Department of Thoracic Medicine, Rajiv Gandhi Government General Hospital and Madras Medical College, for his valuable guidance in writing and reviewing my dissertation.
I am bound by ties of gratitude to Assistant Professors Dr. Ammaiyappan, Dr. V. Sundar, Dr. N. Murugan, Dr. Arul Kumaran,
Dr. Deepaselvi, Dr. ArunBabu, Dr. Palaniyappan, Dr. Veena, Dr. Anbarasi, Dr. Rajeswari, Dr. Vijayachandar.
I would like to thank my seniors especially for guiding me in doing my thesis.
I would like to thank my colleagues and all my juniors for rendering their help whenever I have asked for, in completing my dissertation.
I am profoundly grateful to all the patients, who were subjects of my study for their participation and co-operation.
I thank the Almighty for staying beside me and guiding me through all these years.
CONTENT
SL.
NO
TITLE PAGE NO.
1. INTRODUCTION 1-12
2. REVIEW OF LITERATURE 13-29
3. AIMS AND OBJECTIVE 30
4. MATERIALS AND METHODS 31-44
5. RESULTS 45-69
6. DISCUSSION 70-73
7. CONCLUSION 74-76
8. BIBLIOGRAPHY ANNEXURES ABBREVIATIONS
URKUND PLAGIARISM SCREEN SHOT PLAGIARISM CERTIFICATE
ETHICAL COMMITTEE APPROVAL ORDER CONSENT FORM
PROFORMA MASTER CHART
1
INTRODUCTION
BRONCHIECTASIS is a disease characterised by permanent dilatation of Bronchi and Bronchioles caused by destruction of airway smooth muscle and elastic structures,resulting from or associated with chronic necrotising infections. Bronchiectasis is a chronic lung disorder characterised by recurrent cough, sputum production and recurrent respiratory infections (1).
Pathologically,In Bronchiectasis(bronchos-airway; ectasia-dilatation) there is permanent dilatation of one or more bronchi with failure of the normal mucociliary escalator leading to chronic airway inflammation and chronic bacterial colonisation. This thought have evolved from Laennac original description in 1819 of ectatic bronchi in pathological specimens (2).Bronchiectasis was disabling and fatal disease in pre-antibiotic era.Still,it remains an important cause of suppurative lung diseases in developing world.
Increasing recognition of the disease and improved diagnosis due to advances in computed tomography make bronchiectasis a disease of increasing importance. Recent data from the United States Medicare database found an annual increase in claims for bronchiectasis of 8.7% between 2000 and 2007 (3). The Data also shows increased hospitalisations rate for bronchiectasis between 1993 and 2006 emphasising the growing recognition of this disease (3). Very sparse data is available in india about Bronchiectasis etiology, prevalence and its impact.
2
With available studies(4), the most common cause of Bronchiectasis were
• Tuberculosis(35.5% ),
• Post infectious(22.4%)
• Idiopathic(21.4%)
• Allergic bronchopulmonary aspergillosis( 8.9% )
• Chronic obstructive pulmonary disease( 5.3%)
• Asthma(2.5% )
• Rheumatoid arthritis( 1.8%)
• Primary ciliary dyskinesia(<1% )
• Gastro-esophageal reflux disease( <1%)
• Non-tuberculous mycobacteria(<1% ) and
• Miscellenous(<1%).
3
Etiology of Bronchiectasis in the Indian Bronchiectasis registry
4
DISEASE ASSOCIATIONS AND RISK FACTORS:
The most common etiology of Bronchiectasis in India is Tuberculosis.In this scenario, Bronchiectasis may manifest in following three situations:
Bronchiectasis occurring as a sequele in case of treated pulmonary tuberculosis patients
Bronchiectasis in active case of tuberculosis
Tuberculosis occurring in already diagnosed case of Bronchiectasis Proposed etiopathological evolution could be due to Tuberculous bronchitis resulting from exudative spillage of tuberculous foci or ruptured lymphnode into bronchial tree.This leading to epithelial damage,hamper ciliary motility &
mucus gland secretions,subsequently weaking elastic and smooth muscular bronchial components resulting surrounding contraction of connective tissue
POST-INFECTIVE:
This comprises second majority of cases,in which primary infective insult occurs in childhood and adolescents manifesting as bronchiectasis in later life.This is mainly due to epithelial denudation,ciliary loss leading to bronchiolitis,further secondary infection results in chronic inflammation and vice versa.Careful history of any exanthematous fevers, repeated respiratory tract infections since childhood helps in diagnosis.The causes are:
5
• Measles
• Adenovirus
• Pertussis
• Pneumonia
IDIOPATHIC:
In this scenario,known cause of Bronchiectasis were excluded.Genotypic studies reveals Allelic Polymorphism for HLA-B(B5& B5-2);HLA-C(Cw*03) and HLA-DR/DQ are statistically associated with idiopathic Bronchiectasis (5),which has characteristic phenotype of bilateral lowerlobe Bronchiectasis and chronic rhinosinusitis. Proposed hypothesis is that impaired HLA predisposition results in increased Natural Killer cells activity may leading to chronic inflammation(6).
ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS:
With predisposing factors such as poorly controlled asthmatics,Aspergillus fumigatus ,an ubiquitous fungi will cause this hypersensitivity lung disease.This is characterised by central bronchiectasis often with mucoid impaction in medium sized bronchi. The inflammation and distention typically results in thin-walled bronchiectasis of the central airways.This is one of the treatable etiology of Bronchiectasis .
6
CHRONIC OBSTRUCTIVE PULMONARY DISEASE:
A high prevalence of Bronchiectasis has been demonstrated in an unselected group of patients with a primary care diagnosis of COPD (7), and many studies with alpha-1-antitrypsin deficiency have suggested that bronchiectasis may be present either concomitantly (8) or before the development of emphysema (9,10). Recurrent COPD exacerbations are associated with a heightened airway inflammatory burden, and with the presence of lower airway bacterial colonization, which in turn has been shown to be an independent stimulus to airway inflammation measured by sputum levels of IL-6 and IL-8.
RHEUMATOID ARTHRITIS:
Bronchiectasis was found to be associated with many connective tissue disorders mainly Rheumatoid Arthritis,Primary sjogren syndrome,Systemic Sclerosis,Systemic Lupus Erythematosis and Ankylosing Spondylitis. In Rheumatoid arthritis, Bronchiectasis can occur even before diagnosis of Rheumatoid disease was made.Particularly,in these patients Anti-CCP antibodies was found to be high.
Potential causal mechanisms include increased propensity for infections,either intrinsic to Rheumatoid disease per se or secondary to steroid/cytotoxic therapy.
7
PRIMARY CILIARY DYSKINESIA:
Congenital structural and functional disturbances of the ciliated epithelial cells are seen in association with bronchiectasis,as well as with frequent and severe upper respiratory tract problems .This is an autosomal recessive condition, with an estimated frequency between 1 in 12,500 - 40,000. The ineffective beating of the ciliated cells results in stagnation and accumulation of mucus, resulting in early-onset refractory or recurrent infections of the upper and lower respiratory tract, including otitis media, mastoiditis, sinusitis, and bronchitis.
Bronchiectasisis a common sequela of PCD, typically involving the dependent zones such as lower lobes, right middle lobe,the left lingular segments
RECURRENT ASPIRATION:
This may be due to gastro-esophageal reflux disease and/or dysphagia,which accounts for less than 1.0% cases ,but in western nations it extend upto 11% cases(11).This etiology is less likely considered because as it is common(falsely attributed as casual factor) and asymptomatic for long time.
Neurological problems; oesophageal dysmotility, anatomical abnormalities,fistulaes, post surgical correction may leads to dysphagia resulting in recurrent aspiration.Vocal cord dysfunction may also increase the likelihood of aspiration.
8
CHRONIC SYSTEMIC INFECTIONS:
There is increased risk of Bronchiectasis in chronic infections such as HIV or HTLV 1 (11). Bronchiectasis is found to be associated with Inflammatory Bowel Disease,more occurance with Ulcerative Colitis than Crohns disease.
9
PATHOLOGY
Different pathological mechanisms contribute for producing permanent, pathological dilatation of airways and smooth muscle destruction,which maybe,in general described in following forms:
• Traction
• Pulsion
• Weakend airway tensile strength TRACTION:
Lung patency is contributed mainly by negative intrapleural pressure, large and small airway musculature. Interstitial tethering held effectively by the distending forces of negative intrapleural pressure.Fibrotic lung disorders such as interstitial lung disease, sarcoidosis and tuberculosis causes local retractile forces which leads to fixed airway dilatation termed as “Traction”
PULSION:
This means permanent airway dilatation as result of intense inflammation in lumen and occurs mostly in ABPA,where as hypersensitivity to inhaled fungi results in localised inflammation and damage.
10
AIRWAY TENSILE STRENGTH WEAKNESS:
It comprises of mainly post infective etiology,where more chronic airway damage in structural integrity loss.This will end up in scarring and fibrosis,in turn regional increase in retractile force.The pathological mechanisms revolve mainly around Cole’s hypothesis in which vicious cycle of recurrent or sustained infection and inflammation resulting in Bronchiectasis(13,14)
Figure showing role of neutrophil elastase and other proteolytics leading to chronic inflammation in bronchiectasis.
11
PATHOPHYSIOLOGY:
Lung is constantly exposed to environmental particles,microbes,aerosol materials throughout entire life.Hence,it has well developed defence mechanisms to primarly defend against microbial agents which invade intact respiratory tract.The defence mechanisms include:
Cough reflex
Mucociliary escalator
Antibicrobial peptides (lysozymes,defensins,cathelicidins) Secretory immunoglobulins(IgA)
Airway epithelial cells
Apart from main pathological factors of bronchiectasis such as primary weakness of airways,physical factors,disturbances in the above said lung defense mechanisms will leads to vicious cycle of recurrent or sustained inflammation.The transmural inflammation characterised by infiltration of neutophils,monocytes,lymphocytes causes bronchial damage and develops increased susceptibility to chronic colonization by certain micro organisms namely,
• Pseudomonas Aerogenosa,
• Non Tuberculous Mycobacterium,
• Aspergillus
12
Muco ciliary clearance is an important defence mechanisms against microbial agents in airways.In case of Cystic fibrosis and Pimary Ciliary Dyskinesia,Bronchiectasis occurs mainly due to defective mucociliary clearance(12).Hence,abnormal mucus and ciliary dysmotility herald sufficient microbiological clearance,thus increasing the risk of chronic inflammation.To counter this vicious cycle of inflammation and infection,a robustic immunological response occurs with release of many inflammatory cytokines and chemokines such as IL-8,TNF-alpha,MIP-2 producing airway epithelial damage and mucosal abrasions, mainly by proteolytic enzymes such as Matrix Metalloproteinases and Neutrophil Elastase
Neutrophil elastase and other proteolytic enzymes cleave Fc gamma r receptors and complement receptor 1 from neutrophil surfaces and digest immunoglobulins,complement proteins from bacterial surfaces.These activities dysregulate opsonisation,decrease bacterial recognition by neutrophils,finally leading to impaired phagocytosis(15,16) and reduced bacterial killingNeutrophil elastase have shown to cause ciliary dysfunction,mucus gland hyperplasia,increased mucus secretion thus further impairing clearance
13
REVIEW OF LITERATURE
IMPORTANCE OF DEFINING BRONCHIECTASIS SEVERITY:
In olden days,Bronchiectasis was refered to as ‘orphan disease’,but nowadays it is relatively common diseases affecting about 1 in 1000 people in United Kingdom(17).Many common respiratory disorders have their own stratified approach towards optimized management. In COPD, Global initiative formed GOLD guidelines which enables universal follow up. They stratify COPD based on
Symptomatology
Number of exacerbations FEV1.
This stratification(18) helps in defining disease severity and aids in both pharmacological and non pharmacological management of COPD.
In Asthma,GINA guidelines recommends step-wise approach to therapeutic stratigies(19)in which specific treatment is preferred for symptom control.In community-acquired pneumonia,there are many scoring systems in practice for assessing severity and they plan regarding management according to the severity.This practice has shown promising results in correct hospital discharges and in availing empirical antibiotics for those who need(20,21).
Similarly,Idiopathic Pulmonary Fibrosis Severity also achieved through scoring system and prognosis assessed mainly through impaired lung function – TLC(Total lung capacity) and DLCO,(22).From the above discussions,it clearly showed that most of common respiratory problems had their severity
14
assessed by scoring systems and stratified approach towards optimal management.There is no such stratified approach towards bronchiectasis severity and its treatment.And also effective approach requires mainly understanding prognosis.As wide range of therapies are available for bronchiectasis,identification of patients,those who were most likely benefit becomes critical decision.
DEFINING DISEASE SEVERITY IN BRONCHIECTASIS:
Major keyend points used to define Bronchiectasis severity includes the following;
• Mortality
• Hospital admissions
• Frequency of exacerbations
• Symptoms
• Quality of life
• Lung function decline
15
MORTALITY:
Loebinger et al., done a long term study on mortality of Bronchiectasis and also assessed the factors determining survival(23). About 29.7% patients died during follow up,in which about 70.4% cases died due to respiratory cause alone. They concluded that,Bronchiectasis when severe has increased mortality rate. In a multivariate analysis,Mortality predictors were increasing age,Pseudomonas aerogenosa colonisation,male sex,Total lung capacity, Residual volume/Total lung capacity.
Onen et al in 2007 analysed factors related to mortality of about 98 Bronchiectasis patients and concluded that BMI,Age,mMRC scale considered as strongest predictors of mortality with 16% mortality,secondary to bronchiectasis (24)
A recent spanish study by Martinez-Garcia et al established independent predictors of mortality such as FEV 1,Increasing age,Radiological extent( three or more lobes involved in CT),mMRC dyspnoea scale and Pseudomonas colonisation.Mortality due to Bronchiectasis and associated respiratory conditions was nearly 42.9%(25).
16
Goeminne et al studied about 568 bronchiectasis patients in Belgium over a period of six and half years which accounts for 36% mortality,with strongest risk factor being disease associations such as COPD,Lower FEV 1,Presence of Pulmonary Hypertension,colonisation with potentially pathogenic micro organisms(26,27)
HOSPITAL ADMISSIONS:
A Population based study on factors associated with Bronchiectasis leading to Hospital admissions,done by RinghausenFC et al(28) in germany (2005- 2011) has enumerated that admission risk was positively co-related with increasing age peaking in 75-82 years,mostly men. Radiological severity assessed by Bhalla Score has been linked to Hospital admissions according to retrospective analysis done by Roberts et al in new Zealand(29).
From the above literature, we inferred that old age,male gender,radiological extension of Bronchiectasis in CT were main risk factors leading to most of Hospital admissions in a year.Possible other factors include total symptom duration,BMI,Lung function,Inflammatory markers such as ESR,CRP.However BMI was negatively correlated with hospitalisation risk,while mMRC dyspnoea score,inflammatory markers were positively co related
17
EXACERBATIONS:
This is the most important clinical variable determining the disease severity in Bronchiectasis because this has marked influence in patient quality of life,increased health care utilisation and costs,Long term morbidity associated with them(30,31)
However some authors describe frequent exacerbator phenotype which is already described in Chronic Obstructive Pulmonary disease(32) is not uncommon in Bronchietasis,but still promising studies about phenotypes of bronchiectasis are needed
HEALTH RELATED QoL AND SYMPTOM CONTROL:
St.George Questionnaire has been validated by Wilsonet al(33) for assessing Bronchiectasis patients Quality of life and corelates well with clinical vignitte’s such as exacerbation frequency,radiological extent,mMRCdyspnoea score and FEV 1(lung function)
The Leiscester Cough Questionnaire validated in bronchiectasis patients with chronic cough reveals that cough severity directly related to sputum purulence,presence of chronic bacterial colonisation,the cystic or varicose type of bronchiectasis in CT chest.The above mentioned questionnaire has shown
18
modest improvement in quality of life and cough severity was controlled with optimal management(34).
LUNG FUNCTION DECLINE:
The lung function parameters had rapid decline in some subsets of bronchiectasis patients.Martinez-garcia et al followed 76 bronchiectasis patients over one year in terms of regular monitoring of lung function at adequate intervals(30) and concluded that FEV 1 decline can be predicted mainly by three factors such as chronic colonisation with Pseudomonas,Number of exacerbations and those with increased inflammatory markers.Radiologically,bronchial wall thickening was also considered to be other predictors.
MODIFIERS OF DISEASE SEVERITY IN BRONCHIECTASIS:
• Etiology,
• Clinical factors,
• Lung function,
• Radiological abnormalities,
• Genetics,
• Microbiology
• Airway and systemic inflammation.
19
ETIOLOGY:
Many Respiratory disorders including post infective,mainly tuberculosis,auto-immune and allergic disorders have their final common pathway to be bronchiectasis as their sequele.It is well known fact that underlying etiology influences the progression of bronchiectasis and this is extensively studied in two common comorbities such as Chronic obstructive pulmonary disease,Rheumatoid arthritis.Swinson and colleagues studied patients with Rheumatoid arthritis and Bronchiectasis established that total mortality rate was more than seven-times higher than the general population and five-times that observed in Rheumatoid arthritis without Bronchiectasis.These discrepancies cannot be attributed to age, sex or disease duration or severity.The results emphasize importance of co-morbidity in the prognosis of Rheumatoid patients(36). There were also consistent data that COPD-associated Bronchiectasis has a poorer prognosis in terms of mortality.
AIRWAY AND SYSTEMIC INFLAMMATION:
Bronchiectasis is a disorder of airway structural damage, infection and inflammation.The nature of airway damage was illustrated by radiology, lung function.Infection component detailed by microbiology,number of exacerbations where as inflammation,in sense includes both local(airway) and systemic components. Inflammation in the airway lumen is predominantly neutrophil mediated.Studies correlating markers of neutrophil mediated
20
inflammation with disease severity suggests that the neutrophil granule products elastase and myeloperoxidase are significantly elevated in Bronchiectasis(37,38).The degree of bronchial inflammation is directly related to the bacterial load and can be reduced by effective antibiotic therapy(39).Spontaneous sputum elastase,myeloperoxidase,CXCL-8,TNF-a and IL-1b correlated with FEV1% predicted and radiological severity using the Reiff score in our study of 385 patients(39)
In case of systemic inflammation,Bronchiectasis is associated with upregulation of the circulating adhesion molecules ICAM-1, VCAM-1 and E- selectin.Wilson et al.examined 87 patients with bronchiectasis and found a correlation between the traditional inflammatory markers C-reactive protein and white cell count with health-related QoL(40). But,still further studies were warranted for clinical practice using these markers.
GENETICS:
Whole Genome Sequencing,new advanced tool in identification of many primary antibody deficiencies associated with Bronchiectasis(41). This has promising results when done on patients presenting with familial history of primary antibody deficiency, consanguinity, Bronchiectasis associated with herpes viral infection and lymphoma.This new modality helps in discovery of novel causes and potential treatment for patients with antibody deficiency associated with Bronchiectasis(42).
21
Mannose binding lectin (MBL) is an innate immune protein which recognizes cell surface carbohydrates expressed by a wide variety of bacteria, viruses and fungi. MBL activates the lectin complement pathway resulting in opsonisation and phagocytosis of microorganisms leading to resolution of inflammatory response in the lung
However, low expressing MBL genotypes were associated with increased bacterial colonisation, infective exacerbations and hospital admissions, more severe radiological scores, worse quality of life and increased airway inflammation compared to other MBL genotypes(43).
RADIOLOGICAL ABNORMALITIES:
Modified Reiff criteria that grades the severity of dilatation (tubular = 1 point;varicose = 2 points;cystic = 3 points) and the number of lobes involved has been used as a severity scoring for Non cystic fibrosis Bronchiectasis.But this criteria has some limitations,Loebinger showed that the radiological factors most associated with prognosis were bronchial wall thickening,mucous plugging,mosaic attenuation and emphysema,criteria not included in the modified Reiff criteria (23)
The other radiological scoring system,Bhalla score has been validated in Bronchiectasis, correlating with prognosis and disease severity(44).This takes into account additional parameters including bullae,airway thickening,mucous plugging,consolidation/collapse and emphysema
22
Devaraj et al. demonstrated that diameter of pulmonary artery vasculature as a radiological measure of pulmonary hypertension and was a powerful predictor of mortality independent of confounders (45).
MICROBIOLOGY:
Micro-organisms undergo diverse adaptations to permit chronic infection of the lower respiratory tract.The immune evasion strategies of 3 important pathogens which play an important role in Bronchiectasis are discussed briefly below
Pseudomonas aeruginosa:
Persistent infection with P.aeruginosa is a major clinical problem in severe non-CF Bronchiectasis,associated with a more rapid decline in lung function and earlier mortality (23,30).The phenotypic changes from acute to chronic P.
aeruginosa infections include a reduction in invasive virulence factor expression such as flagellae, pili and toxins(46). P.aerugimosa persistence is associated with transformation to a mucoid phenotype.Following hypoxia,Pseudomonas strains expressing mucoid exopolysaccharide are selected and establish themselves within protective environment(47).The ability to form biofilms is central to survival of these organisms within the lung.Biofilms protect bacteria against clearance by the host immune system and also increase resistance to antibiotics(48).Neutrophils have been shown to promote biofilm formation and once established within biofilms.Pseudomonas becomes highly resistant to neutrophil phagocytosis.Pseudomonas within
23
biofilms becomes non-motile,further protecting them from phagocytosis(49).Initiation of biofilm formation is dependent on the process of quorum sensing.As the number of bacteria within the lung increase, the concentrations of signalling molecules such as homoserine lactones increase.
These diffuse freely into bacterial communities allowing organisms to sense the local population density.Once a critical mass of organisms is reached,quorum- sensing molecules induce gene expression that promotes biofilm formation(50).The hypermutable nature of pseudomonas gives rapid adaptation to environment of lung.Pseudomonas can quickly express or inactivate genes but also increases the frequency of mutation events within its genome to ensure survival in the face of multiple environmental(hypoxia,ionic strength), immune(neutrophils,complement),and antimicrobial challenges.
Haemophilus influenza:
H. influenzae is the most frequent pathogen causing chronic infection in non- CF bronchiectasis and chronic obstructive pulmonary disease.It is also a frequent commensal of the upper respiratory tract in healthy people.H.influenzae can survive intracellularly within macrophages and invade bronchial epithelial cells(51).H.influenzae therefore has both intracellular and extracellular niche within the respiratory tract.King et al.(2003) found evidence of an abnormal Th2 cytokine response to H.influenzae infection with reduced expression of CD40 ligand in Bronchiectasis.The mechanism of this abnormal
24
cytokine response is still unkown.H. influenzae are also able to form biofilms to evade host immune responses(52).
Staphylococcus aureus:
S.aureus is a major clinical problem,particularly in children and is also associated with ABPA or atypical CF in adults with Bronchiectasis.Similar to Pseudomonas,S.aureus downregulates virulence factors during conversion to chronic infection and can form biofilms (53).The ability to form small colony variants (SCV’s) is an important feature of S. aureus virulence.These variants are able to invade and persist within epithelial cells and are remarkably resistance to antibiotics(54).Their role in non-CF Bronchiectasis is not known.
Under anaerobic conditions,which can occur in poorly ventilated areas of the lung,S.aureus forms a polysaccharide intercellular adhesin that protects cells from neutrophil phagocytosis (55).
LUNG FUNCTION DECLINE:
Three important factors responsible for rapid decline of lung function involves:
Chronic sputum colonization with Pseudomonas, Frequent severe exacerbations
Marked systemic inflammation
25
Available long-term management strategies including use of long-acting inhaled bronchodilators,inhaled or oral steroids,oxygen therapy,or antibiotics had a lasting, significant effect on FEV1 decline.The observed annual decline in FEV1 of 52.7mL per year (2.35% per year) mirrors the results reported by Nicotra et al(56) in a group of 38 male and 85 female adult nonsmokers with non-CF Bronchiectasis who showed an annual decline of 55 mL per year in FEV1 but some authors believe that intensification of anti-Pseudomonal treatment in Bronchiectasis cases such as with increased doses, longer duration,or combination therapy possibly could slow or even stop the impairment of lung function over the longer term.However,it is imperative to consider that patients colonized with Pseudomonas experience more bronchial inflammation despite the multiple treatments aimed at eradicating it.
There was heightened inflammation during exacerbations which decreases with antibiotic treatment,but it does not disappear entirely(57).This may be the cause of the greater functional deterioration because of vicious cycle of inflammation and infection observed in bronchiectasis patients with multiple severe exacerbations.
Increased levels of CRP and ESR has greater functional deterioration may be explained by the repeated exacerbations,in turn poor control of disease that was being related to more severe forms of disease.This is associated with
26
increasing loss of pulmonary function as an indicator of Bronchiectasis severity.This proposal has some limitations because of non specificity of both ESR and CRP as systemic inflammatory indices, as their concentrations may be elevated by various diseases or in acute periods in the evolution of the Bronchiectasis.
NEED FOR SEVERITY ASSESSMENT:
Three recent randomized controlled trials have suggested that macrolides taken for 6–12 months reduce the frequency of exacerbations in patients with Bronchiectasis (58,59,60)
EMBRACE trial
The Bronchiectasis and Long-term Azithromycin Treatment trial The Bronchiectasis and Low-dose Erythromycin Study
Above three trials shows a clear benefit from macrolide therapy on rates of exacerbation in specific population with Bronchiectasis and repeated exacerbations
Considering side effects and antibiotic resistance,risk/benefit ratio for macrolides is not clearly mentioned and hence warrents need to identify patients most likely to benefit from long-term treatment.The BTS guidelines
27
for Bronchiectasis,recommends considering long term macrolide treatment in patients with three or more exacerbations in their previous year
A randomized controlled trial of nebulized Gentamicin done in Edinburgh randomized 27 patients to gentamicin 80 mg twice daily and 30 patients to twice-daily 0.9% saline for one year[81].The inclusion criteria enrolled patients with chronic colonization with pathogens, including three positive sputum samples in the past 1 year,at least two exacerbations in the previous year and an FEV1 greater than 30% predicted.The study enrolled patients with P.
aeruginosa but also patients colonized with other pathogens.The primary outcome showed a significant reduction in bacterial density,not only in terms of bacterial load,but also in eradication of pathogens(61).
Treatment was also associated with a significant decline in exacerbations,improved quality of life and cough severity using the Leicester cough questionnaire,improved exercise capacity and reduced sputum purulence.These benefits were substanciated by reduction in markers of neutrophil-mediated inflammation
28
MONITORING:
Improved risk stratification could be helpful in classifying bronchiectasis patients,those who requires long-term follow-up in secondary care and to assess whether patients can be managed safely in primary care.The BTS guidelines currently recommend secondary care management for patients with chronic colonization with P.aeruginosa as well as those who have opportunistic mycobacterial colonization or colonization with MRSA.Bronchiectasis patients should also be seen in secondary care if their lung function is declining,if they have three or more exacerbations per year and are on long-term oral or nebulized antibiotic treatment for prophylaxis.
29
CLINICAL VARIABLES
FEATURES OF MILD BRONCHIECTASIS/GOOD PROGNOSTIC FACTORS
FEATURES OF SEVERE BRONCHIECTASIS/POOR PROGNOSIS
Microbiology No pathogens/H.influenze colonization
Pseudomonas aerogenosa MRSA
Enteric gram negative pathogens
Higher bacterial load
Radiological extent
< 3 lobes involvement Tubular bronchiectasis
>3 lobes involvement Cystic dilatation
Bronchial wall thickening Mosaicism,emphysema
Lung function tests Normal
Airflow obstruction Restriction
Increased RV/TLC
Dyspnoea Grading Grade 0 mMRC grade 4/5
Symptomatology
<5 ml sputum volume Mucoid or mucopurulent sputum
Mild cough or cough only with exacerbations
>25 ml/day sputum production Purulent sputum
Severe cough
Co-morbidities No comorbidity
COPD
Rheumatoid Arthritis associated Bronchiectasis
Exacerbations Frequency
<3 per year
3 or more exacerbations/year Severe exacerbations requiring hospital admissions
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AIMS AND OBJECTIVES
Primary Objective:
Comparison of severity of non cystic fibrosis Bronchiectasis patients by the two prognostic Scores-FACED and Bronchiectasis Severity Index.
Secondary Objective:
To access the exacerbation frequency over one year followup.
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MATERIALS AND METHODS
STUDY DESIGN:
Prospective observational study.
STUDY PERIOD:
12 months from March 2018 to April 2019
SAMPLING METHOD :
Done by Consecutive sampling method.
STUDY CENTRE:
Rajiv Gandhi Government General Hospital, Park Town, Chennai
SUBJECT SELECTION:
Inclusion criteria:
Patients attending thoracic medicine OP of RGGGH and diagnosed as a case of BRONCHIECTASIS by High-Resolution Computerised Tomography chest
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Patients willing to participate in the study and given informed written consent.
Exclusion criteria:
• Not willing for the written informed consent for the study.
• Active pulmonary tuberculosis cases
• Interstitial lung diseases
• Immuno compromised patients
• Patients on long term antibiotic therapy
SAMPLE SIZE:
100 patients who were diagnosed as BRONCHIECTASIS and those who satisfied the inclusion and exclusion criteria were enrolled in the study.
DATA COLLECTION:
The data were collected from the patient are:
• Name
• Age
• Sex
• Height/Weight
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Detailed clinical history was collected which included
History of cough with expectoration and wheeze with their duration.
History of exacerbations and hospitalization in the past 1 year
(exacerbations when patient needed to attend a health care setup because of symptoms which lead to increase in the dose or addition of a
medication )
History regarding severity of symptoms as obtained by Modified Medical Research Council grades(mMRC)
Previous history of co-morbid illness like diabetes mellitus,hypertension.
Smoking history
Previous History of Hospitalisations in Previous 12 months History of wheeze
History of recurrent respiratory tract infections since childhood History of exanthematous fever episodes in childhood
History of aspiration,dyspepsia,dysphagia History of joint pains,early morning stiffness
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STUDY PROTOCOL:
About 126 BRONCHIECTASIS patients who attended Thoracic Medicine Department in Rajiv Gandhi Government General Hospital with repeated complaints of cough with expectoration,breathlessness,atypical chest pain with or without fever has been analysed.
All patients were explained in detail the purpose and methods of study and Informed written consent obtained.Consecutively,these patients subjected to Inclusion and Exclusion Criteria. Hence total of about 100 patients got enrolled in our study.Diagnosis of bronchiectasis was confirmed radiologically by High Resolution Computed Tomography of Chest.Afterwards each patient details were entered in Profoma which includes general characteristics as well as clinical history.Necessary investigations such as Pulmonary function tests,Sputum culture and Sensitivity,Body mass Index,Radiological extent as seen in High Resolution Computed Tomography of Chest and also previous records of hospitalisations in past 12 months,if any and number of exacerbations was noted.
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Individually in all study participants,FACED score obtained,then BRONCHIECTASIS SEVERITY INDEX was also calculated by details provided from investigations above. Statistical analysis of comparision,agreement between the two scores was done.The total study participants were followed up for a period of about one year from the date of enrolment of the study.Exacerbations during this one year was noted in view of outpatient or inpatient management.
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MATERIALS
High Resolution Chest Tomography features of BRONCHIECTASIS:
DIRECT SIGNS:
Bronchiectasis is defined by bronchial dilatation as suggested by one or more of the following:
• Bronchoarterial ratio >1(internal airway lumen vs adjacent pulmonary artery)
• Lack of tapering
• Airway visibility within 1cm of costal pleural surface or touching mediastinal pleura.
INDIRECT SIGNS:
• Bronchial wall thickening
• Mucus impaction
• Mosaic perfusion/air trapping on expiratory CT chest
Radiological extent of Bronchiectasis,was considered according to the number of pulmonary lobes affected( lingula as independent lobe) and the degree of bronchial dilatation described by figure below(tubular,varicose or cystic).A small bronchiectatic changes can be seen in single pulmonary segment and it
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was not considered,as this can be normal finding significant proportion of the healthy population.
Diagram showing various degree of bronchial dilatation
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ASSESSMENT OF SYMPTOMS:
Severity of symptoms as perceived by the patient was assesed using Modified Medical Research Council grades (mMRC)
Modified Medical Research Council grades (mMRC) :
Modified medical research council scale was used to assess the severity of dyspnoea. It quantifies the disability associated with breathlessness by identifying when does the breathlessness occurs(Grades 0 and 1)or by quantifying the associated exercise impairment (Grades 2–4).The mMRC grades were self-administered asking patients to choose the description that best suited to their condition.
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Table : Modified Medical Research Council grades
GRADE DESCRIPTION
0 I only get breathless with strenuous excersice
1 I get short of breath with hurrying on the level or walking up a slight hill
2 I walk slower than people of the same age group on the level because of breathlessness or have to stop for breath when walking at my own pace on the level
3 I stop for breath after walking about 100 yards or after a few minutes on the level
4 I am too breathless to leave the house or I am breathless when dressing
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PULMONARY FUCTION TESTS:
Pulmonary function test was done for all patients who were enrolled.The test was performed in accordance with the criteria set by American Thoracic Society using Easyone Spirometer. The instrument was calibrated daily as recommended.The procedure was explained to all the patients clearly before the test is done.Any recent history of smoking,illness,medications were enquired and the height and weight of the patient was recorded. All participants were kept in the sitting posture for the procedure.All participants were instructed and demonstrated to hold the head in slightly elevated manner,position the mouthpiece and close the lips,inhale completely and rapidly and then exhale maximally until no more air can be expelled out.
Instructions were repeated as necessary.Throughout the manoeuvre,subjects were encouraged to blast out and exhale using appropriate body languages and phrases.The test was stopped whenever they complained of distress or dizziness.The test was repeated till at least three trials with two acceptable and reproducible tests for both FEV1 and FVC were obtained. Measurements were made before and after at least 15 minutes of two puffs of salbutamol (200 microgram) administered using metered dose inhaler with a volumetric spacer.The degree of airflow obstruction was assessed using GOLD guidelines.
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Table : Severity of airflow limitatioin as per GOLD guidelines
GOLD 1 MILD FEV 1>80% PREDICTED
GOLD 2 MODERATE 50%<FEV 1<80% PREDICTED
GOLD 3 SEVERE 30%< FEV1<50% PREDICTED
GOLD 4 VERY SEVERE FEV1< 30% PREDICTED
BODY MASS INDEX:
Body Mass Index (BMI) was calculated from the height and the weight of the patient using the formula
BMI = Weight in kg / (Height in m)²
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Table : Interpretation of nutritional status using BMI
SPUTUM CULTURE:
Bacteriological status of the patients was assessed on spontaneous early- morning sputum samples.Chronic colonization was considered by isolation of potentially pathogenic bacteria in sputum culture on at least two occasions in a period of 3 months (62) as the predominant pathogen underwent bacterial growth most frequently over this period of time.Patients who were unable to provide sputum samples(e.g.due to absence of productive cough)were classified as non-colonized.
BMI NUTRITIONAL STATUS
< 18.5
UnderWeight
18.5-24.9 Normal
25-29.9 Overweight
>30 Obese
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BRONCHIECTASIS SEVERITY INDEX:
Variable <50(0 point) 50-69 (2 points)
70-79( 4 points)
>80 (6 points)
BMI (kg/m2) < 18.5
(2 points)
18.5-25 (0 points)
26-30 (0 point)
>30 (0 point) FEV1% predicted > 80
(0 points)
50-80 ( 1 point)
30-49 (2 points)
< 30 (3 points) Hospital admission
within 2 years
No (0 points)
Yes (5 points)
No.of exacerbations in previous 12 months
0 ( 0 points)
1-2 (0 points)
>3
( 2 points) mMRC dyspnea scale 1-3
( 0 point)
4 (2 points)
5
(3 points) P.Aeruginosa
colonization
No ( 0 point)
Yes (3 points) Colonization with other
organisms
No (0 points)
Yes (1 points) Radiological severity <3 lobes
affected (0 points)
>3 lobes or cystic
Bronchiectasis in any lobe ( 1point)
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FACED SCORE
FEV1% predicted <50(2 points) >50 (0 Points)
Age(years) < 70 (0 point) >70( 2 points)
Colonization by P.aeroginosa No ( 0 point) Yes( 1 point)
Radiological extent of Bronchiectasis
1-2 lobes (0 points) > 2 lobes ( 1 point)
Modified MRC dyspnea scale 1-2 ( 0 points) 3-4 (1 points)
General Characteristics:
1.AGE DISTRIBUTION:
The mean age (SD) of the study participants was 49.10 years .
The mean age (SD) for males was 46.64 years and for females 51.04 years.
0 10 20 30 40 50 60
<50 51
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RESULTS
General Characteristics:
1.AGE DISTRIBUTION:
The mean age (SD) of the study participants was 49.10 years .
The mean age (SD) for males was 46.64 years and for females 51.04
1.Diagram showing age distribution:
50-69 70-79 >80
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39
9
1
The mean age (SD) of the study participants was 49.10 years . The mean age (SD) for males was 46.64 years and for females 51.04
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2.GENDER DISTRIBUTION:
Gender based analysis showed that majority of males 56.8 % and females 46.4 % were of less than 50 years age category .
More than half of the study participants about 56 %were females.
Tab.1: Age and sex wise classification of the study subjects (n=100)
Age category (Years)
Males Females Total
Frequency Percentage
Frequency Percentage
Frequency Percentage
<50 25 56.8 26 46.4 51 51
50-69 17 38.8 22 39.3 39 39
70-79 2 4.5 7 12.5 9 9
>=80 0 0 1 1.8 1 1
Total 44 100 56 100 100 100
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Figure showing Gender distribution of the study participants
44%
56%
Males
Females
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3)BODY MASS INDEX DISTRIBUTION:
The mean(SD) BMI score of the study subjects was 23.3 .About 19 patients were underweight,that includes 11 females and 8 males.Majority,48 patients fall with normal range.Obese patients comprises 12% of total population.
Tab 2:Body Mass Index wise classification of the study subjects(n=100)
BMI Males Females Total
Frequency Percentage
Frequency Percentage
Frequency
Percentage
Underweight 8 18.2 11 19.6 19 19
Normal 21 47.7 27 48.2 48 48
Preobeses 8 18.2 13 23.2 21 21
Obeses 7 15.9 5 8.9 12 12
Total 44 100 56 100 100 100
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Figure showing Body Mass Index wise classification of the study subjects(n=100)
18.20% 19.60%
47.70% 48.20%
18.20%
23.20%
15.90%
8.90%
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
Male Feamle
Underweight Normal range Preobeses Obeses
4) mMRC GRADING OF DYSPNEA:
The severity of breathlessness was graded based on mMRC (modified Medical Researsh Council) grading of dyspnea.
divided into two categories,those with dyspnoea severity grading group with >2 mMRC d
< 2 was 61% and with dyspnoea grade > 2 was 39% respectively.
Tab 3: mMRC grading of dyspnea severity of study participants:
mMRC grade <2
>2
Diagram showing dyspnoea grading distribution:
0 10 20 30 40 50 60 70
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mMRC GRADING OF DYSPNEA:
The severity of breathlessness was graded based on mMRC (modified Medical sh Council) grading of dyspnea.The total 100 study participants were divided into two categories,those with dyspnoea severity grading < 2,the other group with >2 mMRC dyspnoea severity.The percentage of patients with grade
< 2 was 61% and with dyspnoea grade > 2 was 39% respectively.
: mMRC grading of dyspnea severity of study participants:
Male Female Frequency
19 42 61%
25 14 39%
Diagram showing dyspnoea grading distribution:
>2 <2
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The severity of breathlessness was graded based on mMRC (modified Medical The total 100 study participants were
< 2,the other severity.The percentage of patients with grade
: mMRC grading of dyspnea severity of study participants:
Frequency
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5) DEGREE OF AIRFLOW LIMITATION:
In our study, 7 patients had mild airflow limitation (>80% predicted). 39 patients had moderate limitation(50-80% predicted),and 45 cases with severe air flow limitation(30-49% predicted).Nine patients had very severe limitation(<30% predicted)
Tab 4 : Degree of airflow limitation
Degree of airflow limitation
Frequency %
Mild >80% predicted 7
Moderate 50-80% predicted 39
Severe 30-49% predicted 45
Very severe <30% predicted 9
Diagram showing distribution about degree of airflow limitation:
0 5 10 15 20 25 30 35 40 45
>80 7
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Diagram showing distribution about degree of airflow limitation:
50-80 30-49 <30
39
45
9
Diagram showing distribution about degree of airflow limitation:
6) PREVIOUS HOSPITALISATON IN THE STUDY Out of 100 study population,
past, 27 patients had more than or equal to one hospitalization in the past 12 months.
Tab 5: Distribution of patients by previous hospitalization
No.of hospitalizations
0
>1
Diagram showing previous hospital admissions distribution:
0 10 20 30 40 50 60 70 80
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PREVIOUS HOSPITALISATON IN THE STUDY POPULATION:
Out of 100 study population,73 patients didn’t have any hospitalisation in the 27 patients had more than or equal to one hospitalization in the past 12
5: Distribution of patients by previous hospitalization
Male Female %
36 37 73
8 19 27
Diagram showing previous hospital admissions distribution:
0 >1
73
27
POPULATION:
y hospitalisation in the 27 patients had more than or equal to one hospitalization in the past 12
5: Distribution of patients by previous hospitalization
%
73
27
Diagram showing previous hospital admissions distribution:
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7) EXACERBATIONS FREQUENCY IN PREVIOUS YEAR:
Exacerbations in previous year is considered most important factor in assessing disease severity.About 52 patients(28 males & 24 females)had 0-2 exacerbations in previous year,where 48 of them (16 males & 32 females)had >
3 exacerbations in last year.
Tab 6:Distribution of patients by number of exacerbations in previous years:
Exacerbations frequency/ previous yr
Male Female %
0-2
28
24
52
3
16
32
48
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Diagram showing distribution of exacerbations frequency:
52
48
46 47 48 49 50 51 52 53
0-2 >3
8) PSEUDOMONAS COLONISATION:
Out of 100 study population,only 13 has chronic
pseudomonas aerogenosa where as remaining patients does not have pseudomonas colonization.
Tab 7:Distribution of patients by pseudomonas colonization:
Pseudomonas colonisation
Yes
No
Diagram of pseudomonas distribution among study group:
0 10 20 30 40 50 60 70 80 90
present
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PSEUDOMONAS COLONISATION:
Out of 100 study population,only 13 has chronic colonization pseudomonas aerogenosa where as remaining patients does not have pseudomonas colonization.
7:Distribution of patients by pseudomonas colonization:
Pseudomonas
Male Female %
6 7
13
38
49
87
Diagram of pseudomonas distribution among study group:
present absent
13
87
colonization with pseudomonas aerogenosa where as remaining patients does not have
7:Distribution of patients by pseudomonas colonization:
%
13
87
Diagram of pseudomonas distribution among study group:
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Values of the FACED score variables
Table 2.1. Values of the FACED score variables (n=100)
Variable Male (%) Female (%) Total (%) FEV1 % predicted
< 50%
> 50%
25(56.8) 19(43.2)
18(32.1) 38(67.9)
43(43) 57(57) Age (yrs)
< 70 >70
42(95.5) 2(4.5)
48(85.7) 8(14.3)
90(90) 10(10)
Chronic colonization by Pseudomonas aeruginosa
No yes
38(86.4) 6(13.6)
49(87.5) 7(12.5)
87(87) 13(13)
Radiological extent (HRCT) > 2 lobes affected < 2 lobes affected
20(45.5) 24(54.5)
17 (30.4) 39(69.6)
37(37) 63(63) mMRC dyspnea score
> 2 (II) < 2 (II)
25(56.8) 19(43.2)
14(25) 42(75)
39(39) 61(61)
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FACED SCORE:
Table2.1 showing Distribution of the study subjects by the FACED score (n=100)
FACED score
Male Female Total
n ( %) n ( %) n ( %)
Mild Bronchiectasis
(0-2 score) 26 (59.1) 18 (32.1) 44 (44)
Moderate Bronchiectasis
(3-4 score) 12 (27.3) 25 (44.6) 37 (37)
Severe Bronchiectasis
(5-7 score) 6 (13.6) 13 (23.2) 19 (19)
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Diagram showing Distribution of the study subjects by the FACED score
44%
37%
19%
Mild Bronchiectasis Moderate Bronchiectasis Severe Bronchiectasis
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BRONCHIECTASIS SEVERITY INDEX:
Tab 3.1 .Values of the BSI variables.
Variable Male Female Total
n (100) n (100) n (100) Age (yrs)
< 50 50-69 70-79 > 80
25 (56.8) 17 (38.6) 02 (4.05) 0
26 (46.4) 22 (39.3) 07 (12.5) 01 (1.08)
51 (51) 39 (39) 09 (09) 01 (01) BMI (kg / m2)
> 18.5 < 18.5
37 (84.1) 07 (15.9)
45 (80.4) 11 (19.6)
82 (52) 18 (18)
FEV1 % predicted > 80%
50-80%
30-49%
< 30%
06 (13.6) 20 (45.5) 16 (36.4) 2 (4.5)
01 (1.8) 19 (33.9) 29 (51.8) 07 (12.5)
07 (07) 39 (39) 45 (45) 09 (09)
Hospital admission in previous year
No Yes
36 (81.8) 08 (18.2)
37 (66.1) 19 (33.9)
73 (73) 27 (27)
Exacerbations in previous year 0-2
>3
28 (63.6) 16 (36.4)
24 (42.9) 32 (57.1)
52 (52) 48 (48) mMRC dyspnea score
1-3 4
42 (95.5) 0 2 (4.5)
48 (85.7) 08 ( 14.3)
90 (90) 10 (10)
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Pseudomonas aeruginosa colonization
No Yes
37 (84.1) 07 (15.9)
49 (87.5) 07 (12.5)
86 (86) 14 (14)
Colon ization with other microorganisms
No Yes
32 (72.7) 12 (27.3)
31 (55.4) 25 (44.6)
63 (63) 37 (37)
Radiological extent (HRCT)
> 3 lobes affected or cystic Bronchiectasis
No Yes
23 (52.3) 21 (47.7)
24 (42.9) 32 (57.1)
47 (47) 53 (53)
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Table 3.2showing BSI score in study participants:
BSI score Male Female Total
n ( %) n( %) n( %)
Low BSI Score (0-4)
21(47.7) 12 (21.4)
33 (33)
Intermediate BSI Score (5-8)
11(25) 15(26.8)
26 (26)
High BSI Score (9 & more)
12(27.3) 29(51.8) 41 (41)
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Figure showing distribution of the study subjects by the BSI score
33%
26%
41%
Low BSI ScoreIntermediate BSI Score High BSI Score
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COMPARISION OF FACED SCORE AND BRONCHIECTASIS SEVERITY INDEX:
While comparing the values obtained by FACED and BRONCHIECTASIS SEVERITY INDEX,a Separate Mean score was calculated for each score and found that the mean score of BSI was more than FACED score.This difference was found to be statistically significant with the p value of < 0.001.
Figure showing Comparison of FACED and BSI mean scores
0 1 2 3 4 5 6 7 8 9
BSI score FACED score
Mean with SD
7.18 (6.26 -810)
2.71(2.32- 3.10)
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Tab 4.1. Comparison of FACED and BSI mean scores
Score Mean SD t value 95% CI p value
BSI score 7.18 4.620
13.812 3.828 – 5.112 0.001 FACED
score
2.71 1.981
CORRELATION BETWEEN FACED AND BSI SCORE:
There was a significant positive correlation was seen between FACED score and BSI score that is statistically significant with p value of 0.001 and r2 value 0.80.
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AGREEMENT BETWEEN FACED & BSI SCORE :
There was a moderate agreement between FACED and BSI score in predicting severity of Bronchiectasis with the cohen’s Kappa value of 0.545 at p value
<0.001 which is statistically significant.
Tab.4.1. Agreement between FACED and BSI score
BSI score
FACED Score Total Kappa value
P value
Mild Moderate Severe
Low 32 0 0 32
0.545 <0.001
Intermediate 7 19 1 27
High 5 18 18 41
Total
44 37 19 100
