GRADE-ADOLOPMENT of clinical practice guidelines and creation of clinical pathways for the primary care management of chronic respiratory conditions in Pakistan.

INTRODUCTION: In Pakistan, chronic respiratory conditions contribute a large burden of morbidity and mortality. A major reason for this is the lack of availability of local evidence-based clinical practice guidelines (EBCPGs) in Pakistan, particularly at the primary care level. Thus, we developed EBCPGs and created clinical diagnosis and referral pathways for the primary care management of chronic respiratory conditions in Pakistan. METHODS: The source guidelines were selected by two local expert pulmonologists after a thorough literature review on PubMed and Google Scholar from 2010 to December 2021. The source guidelines covered idiopathic pulmonary fibrosis, asthma, chronic obstructive pulmonary disorders, and bronchiectasis. The GRADE-ADOLOPMENT process consists of three key elements: adoption (using recommendations as is or with minor changes), adaptation (effective context-specific changes to recommendations) or additions (including new recommendations to fill a gap in the EBCPG). We employed the GRADE-ADOLOPMENT process to adopt, adapt, adopt with minor changes, or exclude recommendations from a source guideline. Additional recommendations were added to the clinical pathways based on a best-evidence review process. RESULTS: 46 recommendations were excluded mainly due to the unavailability of recommended management in Pakistan and scope beyond the practice of general physicians. Clinical diagnosis and referral pathways were designed for the four chronic respiratory conditions, explicitly delineating the role of primary care practitioners in the diagnosis, basic management, and timely referral of patients. Across the four conditions, 18 recommendations were added (seven for IPF, three for bronchiectasis, four for COPD, and four for asthma). CONCLUSION: The widespread use of the newly created EBCPGs and clinical pathways in the primary healthcare system of Pakistan can help alleviate the morbidity and mortality related to chronic respiratory conditions disease in the country.

Residual symptoms and the quality of life in individuals recovered from COVID-19 infection: A survey from Pakistan.

BACKGROUND: There remains scarcity of literature regarding the patient's health status post-COVID-19 infection. This study analyzes the prevalence of residual symptoms and quality of life (QoL) after COVID-19. METHODS: An anonymous online survey was administrated in Pakistan from November 2020 to April 2021 in COVID-19 survivors. The questionnaire used the 12-Item Short Form Health Survey (SF-12) to assess mental and physical QoL. Multivariate linear regression was used to explore factors associated with mental and physical QoL scores. RESULTS: A total of 331 COVID-19 survivors participated in our survey. Around 42.0% of the cohort reported within 1-3 months of diagnosis of COVID-19. The common residual symptoms were body aches (39.9%), low mood (32.6%), and cough (30.2%). Better physical QoL was associated with being male (adjusted beta: 3.328) and having no residual symptoms (6.955). However, suffering from nausea/vomiting during initial COVID-19 infection (-4.026), being admitted to the ICU during COVID-19 infection (-9.164), and suffering from residual body aches (-5.209) and low mood (-2.959) was associated with poorer QoL. Better mental QoL was associated with being asymptomatic during initial COVID-19 infection (6.149) and post-COVID (6.685), while experiencing low mood post-COVID was associated with poorer mental QoL (-8.253 [-10.914, -5.592]). CONCLUSION: Despite presumed "recovery" from COVID-19, patients still face a wide range of residual symptoms months after initial infection, which contributes towards poorer QoL. Healthcare professionals must remain alert to the long-lasting effects of COVID-19 infection and aim to address them appropriately to improve patients' QoL.

Accuracy of genotype MTBDRplus line probe assay in patients with tuberculous pleural effusion: comparison with clinical and culture based diagnosis.

Background: Pleural tuberculosis (TB) diagnosis is challenging due to paucibacillary disease. Diagnostic accuracy of GenoType MTBDRplus Line Probe Assay (MTBDRplus) has been evaluated in this study for pleural TB diagnosis.Objective: To evaluate diagnostic accuracy of MTBDRplus for pleural TB diagnosis compared to clinical and microbiological diagnosis.Methods: This prospective study was conducted at the Aga Khan University, Pakistan. Pleural fluid from 203 suspected pleural TB patients was collected and tested for smear, culture and MTBDRplus. Diagnostic accuracy of MTBDRplus was determined using clinical diagnosis and culture as the gold standard.Results: Out of 203 TB suspect patients, MTBDRplus, culture and smear were positive in 14 (6. 9%), 27 (13.3%) and 4 (1.9%) cases, respectively. A total of 106/203 patients (27 culture positive and 79 culture negative) successfully completed TB treatment. Considering clinical diagnosis as gold standard, sensitivity of MTBDRplus was 13.2%; 95% CI (7.4-21.2%) and specificity was 100%; 95% CI (96.1-100%). The sensitivity and specificity of MTBDRplus in culture positive samples were 44.4%; 95% CI (25.5-64.7%) and 98.9%; 95% CI (95.9-99.9%), respectively. Excluding indeterminate results, MTBDRplus accurately detected isoniazid sensitivity in 5/6 and rifampicin sensitivity in 6/6 cases.Conclusion: MTBDRplus had a low sensitivity of 13.2% in clinically diagnosed and 44% in culture-confirmed pleural TB patients and therefore could not be included in most diagnostic algorithms. Due to a higher sensitivity than smear, MTBDRplus may have a role in tuberculous pleural effusion diagnosis if it is positive pending culture results and pleural biopsy.

Large mediastinal mass in a 15-year-old boy.

Hyperimmunoglobulin E syndrome is a rare multisystem inherited disorder characterised by high serum IgE levels, skin disorder causing eczema, dermatitis, recurrent staphylococcal infections and pulmonary infections and various skeletal and connective tissue abnormalities. Common presentation is with recurrent skin and sinopulmonary infections. Several features unrelated to immune system such as characteristic facial features, hyperextensibility of joints, multiple bone fractures and craniosynostosis have been described in the literature. We describe a rare presentation of this disease with invasive aspergillosis presenting as mediastinal mass with extension to mediastinal structures and pulmonary vasculature.

Granulomatosis with polyangiitis: a 17 year experience from a tertiary care hospital in Pakistan.

OBJECTIVE: Granulomatosis with Polyangiitis (GPA) is an autoimmune, multi-system, small and medium vessel vasculitis with granulomatous inflammation. Aim of this study was to assess the clinical and radiological presentations of patients with GPA amongst the Pakistani population. It is a single centre retrospective single observation study. RESULTS: Study was conducted at the Aga Khan University Hospital, Karachi with records were reviewed from January 2000 to December 2017. Definitive diagnosis was made using a combination of serological anti-neutrophil cytoplasmic antibody (ANCA) testing along with the clinical and radiological presentation. A total of 51 patients met the diagnostic criteria in the time frame of the study. There were 23 males and 28 females with mean age of 44.0 ± 17.8 years on presentation. Arthritis was the most common symptom present in 41.2% of the cases followed by cough in 32.0%. Sixteen patients showed pulmonary infiltrates on chest X-ray. C-ANCA was positive in all of the patients compared with 21.6% p-ANCA positivity. A total of 13 biopsies were done. The median Birmingham Vasculitis Activity Score was 12. We report a 17.6% mortality rate with 5 deaths occurring due to respiratory failure. GPA is a diagnostic challenge leading to late diagnosis which can contribute to significant morbidity and mortality specially in the Third World.

Clinical characteristics and factors associated with mortality in idiopathic pulmonary fibrosis: An experience from a tertiary care center in Pakistan.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease (ILD) that predominantly affects older adults. IPF has the highest mortality burden of all ILDs. Data on mortality in patients with IPF is limited in developing countries. OBJECTIVES: To identify factors associated with mortality in patients with IPF at a tertiary care center in Pakistan. METHODS: A retrospective chart review was conducted at the Aga Khan University Hospital (AKUH) in Karachi, Pakistan from January 2005 to December 2015. Patients were assessed for smoking status, clinical onset of disease, pulmonary hypertension, disease severity based on spirometry and hypoxemia. RESULTS: A total of 239 cases were reviewed, of which 103 were non-survivors. A total of 45 (18%) were current smokers and 71 (29.7%) were ex-smokers. Smoking was more common in non-survivors (56.3% P ≤ .01). Pulmonary hypertension was present in 18.8% of patients. 95.4% of patients who had received pirfenidone treatment were alive at the time of study. On multivariate analysis, pirfenidone treatment (OR 0.03; 95% CI 0.01-0.08), current smoking (OR 2.60; 95% CI 1.04-6.58), age older than 60 years (OR 2.63; 95% CI 1.04-6.58) and hypoxemia (OR 3.29; 95% CI 1.58-6.84) were the factors associated with mortality. CONCLUSION: Smoking, age greater than 60 years and hypoxemia were identified as factors that increased the odds of mortality in IPF patients, whereas pirfenidone was found to lower the odds of mortality.

A rare cause of recurrent wheeze and seizures.

A 34-year-old woman presented with recurrent attacks of breathlessness and seizures. The patient's condition worsened during the course of her hospital stay, as a result of which she had to be intubated twice. Radiological studies showed a mass in the trachea and the subsequent biopsy of the mass revealed an infiltrating carcinoma with morphological features of adenoid cystic carcinoma.

A rare aetiology of respiratory failure in a 10-year-old boy: inflammatory myofibroblastic tumour.

Primary neoplasms of the respiratory tract are rarely encountered in the paediatric population. Inflammatory myofibroblastic tumour (IMT) is a rare soft tissue mesenchymal tumour but a distinct disease entity accounting for less than 1% of all primary lung tumours. We report a case of a 10-year-old boy who presented with respiratory failure and left lung collapse. On flexible fiberoptic bronchoscopy, a pedunculated mass in the lower part of the trachea originating from the left main stem bronchus was identified. The patient subsequently underwent a left-sided pneumonectomy with complete resection of the mass. The histopathological analysis was consistent with IMT. Two years of follow-up and the patient remains well.

Case series and literature review of multiple nodular sarcoidosis.

BACKGROUND: Nodular lung disease is a rare presentation of sarcoidosis. Radiologically it can present as multiple pulmonary masses or solitary lung nodule. CASE PRESENTATION: We report three cases of nodular sarcoidosis in young females of Asian origin who had initially presented with dry cough and worsening dyspnea non-responsive to initially administered antibiotics. Pulmonary nodules were discovered upon radiographic imaging in all three cases which raised concern for the possibility of neoplastic processes. Subsequent biopsies revealed granulomatous inflammation indicative of sarcoidosis. All cases responded very well to systemic corticosteroids. CONCLUSION: Sarcoidosis may present as nodular infiltrates which alerts the treating physician to other neoplastic and infectious diseases of the lungs. Appropriate workup may reveal the true nature of this disease and hence, simplify treatment.

Cross-sectional study identifying forms of tobacco used by Shisha smokers in Pakistan.

OBJECTIVES: To estimate the frequency of different forms of tobacco intake such as smoker's tobacco, chewable tobacco and snuff tobacco among shisha smoker's and to study the patterns and predictors of shisha smoking affecting youth from different cities of Pakistan. METHODS: A cross-sectional study was conducted including youth from four cities. Participants were asked to fill out a data collection tool at shisha cafes, shopping malls and restaurants. Data was analyzed using SPSSv.18. RESULTS: A total of 406 participants, 296 (73%) males and 110 (27%) females were included in the study. There were 163 (40%) cigarette smokers; 65 (16%) chewed tobacco and 33 (8%) snuffed it. The median age at initiation of Shisha smoking was 20 years. 280 (69%) considered Shisha smoking to be less deleterious to health than cigarettes. Respiratory disease was the most commonly cited health effect reported. Most 248 (61%) of the participants were infrequent shisha smokers. CONCLUSION: There is high frequency of tobacco usage in the form of cigarettes, chewable tobacco and snuff tobacco among shisha smokers of Pakistan. The highest frequency is for cigarette smoking. The rise in Shisha smoking as a trendy social habit appears to be occurring despite emerging scientific evidence of its potential health risks.

Pulmonary talcosis 10 years after brief teenage exposure to cosmetic talcum powder.

Pulmonary talcosis is a rare but debilitating variant of pneumoconiosis often presenting with isolated non-specific symptoms of progressive exertional dyspnoea or cough. Occupational exposure to talc dust and intravenous drug abuse are well-recognised aetiological factors with only a few cases related to cosmetic talc exposure being reported to date. The authors report a case of a young woman in whom a mere 4 month ritual of inhaling cosmetic talcum powder led to full-blown pulmonary talcosis being diagnosed 10 years later. The importance of a taking a pertinent history relating to environmental exposures in all patients presenting with respiratory symptoms is re-established here.

Variables predictive of outcome in patients with acute hypercapneic respiratory failure treated with noninvasive ventilation.

OBJECTIVE: To assess results with NIV in acute hypercapneic respiratory failure and to identify outcome predictors. METHODS: This was a retrospective observational study on consecutive patients presenting with acute type II respiratory failure and meeting criteria for NIV use over a 5 year period. Patients presenting with haemodynamic instability, inability to protect their airway, malignant arrhythmias and recent oesophageal surgery were excluded. Univariate and Multivariate regression analysis was used to determine the impact on survival. A p value of < 0.05 was considered statistically significant. Software used was SPSS 14. RESULTS: Total numbers of patients included were 119; 52.9% were males. Mean age was 63.4 +/- 11.9 years. Overall Survival to discharge rate was 76.5%, intubation rate was 12.6% and mean length of stay was 11.4 +/- 10.9 days. Statistically significant improvements were observed in the pH and PaCO2 at 24 hours and 48 hours compared to baseline (7.28 v/s 7.37, p < 0.001; 74.2 v/s 65, p < 0.001). On multivariate regression analysis, sepsis at admission predicted mortality (adjusted Odds ratio 26.4; 95% CI 2.3, 304, p < 0.009). A serum HCO3 > 35 Meq/L (adjusted Odds ratio 0.9; 95% CI 0.83, 0.98, p < 0.015) identified those less at risk for intubation. CONCLUSION: NIV was found to be both safe and effective in the management of acute hypercapneic respiratory failure. Sepsis and serum HCO3 at admission identified patients having poor outcomes.

Tracheal stenosis mimicking severe acute asthma.

Post-intubation tracheal stenosis is a rare but serious clinical entity that rarely develops when intubation is less than a week. These patients may remain asymptomatic for a variable period and are often misdiagnosed as asthmatic. The authors report a case of a middle-aged lady who was initially misdiagnosed as having acute asthma after brief tracheal intubation.

Osseous spinal sarcoidosis: an unusual but important entity to remember.

Sarcoidosis is a multi-system disorder of unknown aetiology characterised by non-caseating granulomatous inflammation with varying presentation and prognosis. Bone involvement is uncommon and vertebral involvement is rare. We report a case of vertebral osseous sarcoidosis which presented with pulmonary symptoms mimicking tuberculosis and later developed vertebral involvement despite administration of oral corticosteroids.

Clinical characteristics, management and outcome of major pulmonary embolism: an experience from a tertiary care center in Pakistan.

OBJECTIVE: To evaluate the clinical characteristics, risk factors, management and outcome of major pulmonary embolism (PE) in a tertiary care center of Karachi. METHODS: Medical records of all patients who underwent a spiral CT scan of the chest for suspected pulmonary embolism were reviewed between January 2000 and June 2007 at the Aga Khan University Hospital, Karachi. Patients having evidence of major pulmonary embolism on spiral CT scan were selected. RESULTS: A total of 30 patients (10 males, 20 females) with mean age 52 +/- 14.59 years were identified who fulfilled our predefined criteria for major pulmonary embolism. Risk factors for thromboembolism were identified in 22 (73%) patients, prolonged immobilization in 8 (27%) and recent surgery in 8 (27%) patients being the commonest. All patients were symptomatic on presentation. Tachypnea and tachycardia were present in 27 (90%) patients. Refractory hypoxia was present in 18 (60%) patients and 3 (10%) were hypotensive on presentation. On spiral CT scan, 8 (27%) patients had embolus in the main pulmonary trunk, 26 (87%) patients in main right pulmonary artery and 20 (67%) patients had left main pulmonary artery embolus. Echocardiography was done in 22 (73%) patients with the findings of right ventricular dysfunction in all of them. All patients except one were treated with anticoagulation with either heparin infusion or low molecular weight heparin. In addition, thrombolytics were given in 7 (23%) patients and five (17%) underwent surgical embolectomy. Four (13%) patients died during hospitalization with a total of 26 (87%) surviving till hospital discharge. CONCLUSION: Major pulmonary embolism is an uncommon but potentially life threatening entity. Early diagnosis and aggressive therapy improves the clinical outcome.

Wegener's granulomatosis: a diagnostic challenge.

Wegener's Granulomatosis (WG) is a necrotizing granulomatous vasculitis that primarily involves small vessels in the body. Patient usually presents in the fourth to fifth decade. The clinical presentation is variable; however, majority of patients (90%) seek medical attention for nasal and sinus symptoms with or without lower respiratory symptoms of cough, dyspnoea and haemoptysis. The typical form of WG tends to involve the triad of upper and lower respiratory tract and the kidneys; while involvement of other organs like ocular, cutaneous, rheumatological, neural, gastrointestinal and lower genito-urinary tract is occasionally seen. A "limited" form with clinical findings isolated to the upper respiratory tract or lungs, occur in approximately one-fourth of cases. We present a case of Wegener's Gmnulomatosis in an eighty five year old lady who presented with an acute pneumonia-like illness. She underwent an extensive work-up to reach a definitive diagnosis.

Massive hemoptysis as a rare presentation of metastatic choriocarcinoma.

Choriocarcinoma is an uncommon but rapidly invasive and widely metastasizing tumour. Lung is the commonest organ of spread, usually presenting as mild hemoptysis and chest pain in a patient with a recent miscarriage or known molar pregnancy. One such case of a 25 years old woman is reported who did not have any history of recent pregnancy or miscarriage and presented with a life-threatening massive hemoptysis. She responded well to therapy once the diagnosis of metastatic choriocarcinoma was established .

Bronchial carcinoid presenting with abdominal pain.

Bronchial carcinoid tumors are very rare pulmonary neoplasms. They usually present with pulmonary symptoms or paraneoplastic syndromes. Typical (well-differentiated) tumors are usually indolent with survival exceeding 90% after resection. Atypical carcinoids have a worse prognosis. They are much more likely to recur locally or to have distant metastases. This case report describes a patient who presented with abdominal pain and hepatic lesions who was subsequently diagnosed to have bronchial carcinoid.

A case of non-resolving cough and weight loss.

Sarcoidosis is a chronic granulomatous multi-system disease with a clinical picture often mimicking tuberculosis. We present a case of a patient who presented with a clinical picture akin to both of these granulomatous disorders and was started on anti-tuberculous regimen despite the lack of any solid evidence pointing towards tuberculosis. As a result her clinical condition continued to deteriorate for months until finally a bronchoscopic biopsy established her disease process as sarcoidosis. She was then started on systemic corticosteroid therapy for sarcoidosis and during the ensuing period has shown marked improvement in her clinical picture with near normalization of the biochemical and radiographic parameters of her pathology. This case illustrates the need for vigilant interpretation of the clinical scenario in patients such as these where a misdiagnosis may lead to significant patient distress as well as weighing down on the economic and health resources.