Feisal A. Al-Kassimi

Nationwide community survey of tuberculosis epidemiology in Saudi Arabia

In the first nationwide community-based survey of the epidemiology of tuberculosis in Saudi Arabia, 7721 subjects were screened in the 5 provinces (using an equal proportional allocation formula) for 2 parameters: (1) prevalence of positive Mantoux test in non BCG vaccinated subjects; (2) prevalence of bacillary cases on sputum culture. The prevalence of positive Mantoux reaction in children aged 5-14 years was 6% +/- 1.8; higher in urban areas (10%), and lower in rural areas (2%), thus classifying Saudi Arabia among the middle prevalence countries. These relatively good results (by Third World standards) could reflect the rise of the standard of living and wide availability of free treatment for active cases with a lowered risk of infection in the community. This view is supported by the fact that in our survey, only one subject grew Mycobacterium tuberculosis in the sputum. However, there were foci of high prevalence of Mantoux reaction in the urban communities in the Western province (20% +/- 8.7 urban; 1% +/- 1.9 rural). The problem may be caused by the fact that the province receives every year over a million pilgrims, some of whom are known to settle illegally and escape the usual screening for tuberculosis imposed on foreign labourers. In conclusion, even in the absence of an enforceable national programme for the eradication of tuberculosis, the economic standard and wide availability of free treatment for active cases has resulted in relatively low rates of prevalence of tuberculin sensitivity in children. The foci of high prevalence in the Western Province require special screening arrangements.

Prediction of Pulmonary Hypertension in Patients with or without Interstitial Lung Disease: Reliability of CT Findings

PURPOSE To study the reliability of pulmonary vascular measurements based on computed tomography (CT) in the prediction of pulmonary hypertension (PH) in patients with advanced interstitial lung disease (ILD) compared with those without ILD. MATERIALS AND METHODS The study was approved by the Institutional Review Board. All patients gave written informed consent. A prospective study of 134 patients who underwent right-sided heart catheterization and chest CT scanning within 72 hours of admission was conducted. Patients were divided into two groups-one with ILD (group A, n = 100) and one without ILD (group B, n = 34). CT measurements of the main pulmonary artery diameter (PAD), the ratio of PAD to the ascending aorta diameter (AAD), right pulmonary artery diameter (RPAD), and left pulmonary artery diameter (LPAD) were obtained. Univariate logistic regression analysis was performed, and receiver operating characteristic curves were constructed to assess the predictive ability of vascular measurements obtained by using CT in the identification of PH. RESULTS Main PAD was significantly greater in patients with PH than in those without PH in both groups (group A, P = .008; group B, P = .02). A PAD greater than 25 mm in patients with ILD was predictive of PH, with a sensitivity of 86.4% (32 of 37), a specificity of 41.2% (26 of 63), a positive predictive value of 46.3% (32 of 69), and a negative predictive value of 83.8% (26 of 31). In patients without ILD, a PAD greater than 31.6 mm and an LPAD greater than 21.4 mm were predictive of PH (sensitivity, 47.3% [nine of 19]; specificity, 93.3% [14 of 15]; positive predictive value, 90.0% [nine of 10]; and negative predictive value, 58.3% [14 of 24]). CONCLUSION CT-derived vascular measurements were of limited utility in the prediction of PH in patients with ILD compared with those without ILD.

Progressive rise of Mycobacterium tuberculosis resistance to rifampicin and streptomycin in Riyadh, Saudi Arabia.

Objective: The aim of this study was to investigate, for the first time, the factors associated with resistance to antituberculous drugs in Saudi Arabia, and to follow the long‐term trends in drug resistance.

A challenge to the seven widely believed concepts of COPD.

This review proposes a critical reassessment (based entirely on published evidence) of the following seven common beliefs about chronic obstructive pulmonary disease (COPD): (1) COPD is one disease. (2) There is a valid definition for COPD. (The current definition includes cases of irreversible asthma and bronchiectasis, and occasionally, other obstructive lung conditions). (3) Irreversible asthma in smokers and COPD cannot be differentiated. (4) A “chronic bronchitis” form of COPD exists and is characterized by blue bloater status and normal carbon monoxide diffusion studies. (5) Phenotyping has no bearing on medication choice in COPD. (6) Computerized scoring of lung attenuation on CT scans can diagnose emphysema. (Emphysema scores overlap in irreversible asthma and COPD); however, qualitative visual changes may be useful for differentiation. (7) A definable entity called the overlap (of COPD and asthma) syndrome exists. Conflict over the abovementioned points denies patients proper phenotype-guided therapy and encourages a multidrug approach to COPD management. The recently coined term, overlap syndrome, invites a double-barreled therapy aimed at asthma and COPD, despite the absence of any agreement about how to define the syndrome and the lack of any related drug trials (in the area of inhaled corticosteroids). A diagnosis of COPD is associated with high morbidity and escalating costs, suggesting the need for a thorough new examination of the evidence.

Asthma masquerading as chronic obstructive pulmonary disease: a study of smokers fulfilling the GOLD definition of chronic obstructive pulmonary disease.

Background: Irreversible airways obstruction in smokers is usually attributed to chronic obstructive pulmonary disease (COPD). We speculate that some of these are cases of asthma indistinguishable from COPD. Objectives: To determine the prevalence of asthma in a ‘COPD’ population and how to differentiate the two conditions. Methods: This was a prospective observational study of smokers fulfilling the Global Initiative for Chronic Obstructive Lung Disease definition of COPD [mean post-salbutamol forced expiratory volume in 1 s (FEV1) 66.9% predicted]. They were classified into 4 groups, as follows: (1) inhaled corticosteroid (ICS)-responsive asthma, defined by normalization of spirometry upon ICS treatment; (2) irreversible asthma, defined as airway obstruction for 1 year and bronchial biopsy indicating asthma; (3) COPD, in the presence of bilateral panlobular emphysema with bullae on high-resolution computed tomography, hypercapneic respiratory failure or bronchial biopsy indicating COPD, and (4) unclassified airflow limitation (AFL). Results: Eighty patients fulfilled the definition of COPD. The initial diagnosis was COPD in 57.5% and asthma in 42.5%. The final diagnosis was ICS-responsive asthma in 48 patients (60%), irreversible asthma in 8 (10%), COPD in 16 (20%) and unclassified AFL in 8 (10%). A normal transfer coefficient for carbon monoxide (KCO) and an FEV1 fluctuation ≧18% during 1 year of follow-up distinguished irreversible asthma and COPD. Seven of the 8 patients with irreversible asthma had improved FEV1 at the end of 1 year (median 320 ml compared with –29 ml in COPD). Five out of the 8 unclassified AFL cases had normal KCO and a large improvement in FEV1 suggestive of irreversible asthma. Conclusions: COPD, even in heavy smokers, includes cases of asthma. FEV1 fluctuation during 1 year is a novel concept which may distinguish irreversible asthma and COPD.

Abrupt withdrawal of inhaled corticosteroids does not result in spirometric deterioration in chronic obstructive pulmonary disease: Effect of phenotyping?

BACKGROUND AND OBJECTIVE: Some studies show a decline of FEV1 only one month after withdrawal of inhaled corticosteroids (ICS), while others show no decline. We speculate that the presence of an asthma phenotype in the Chronic Obstructive Pulmonary Disease (COPD) population, and that its exclusion may result in no spirometric deterioration. METHODS: We performed a prospective clinical observation study on 32 patients who fulfilled the Global Initiative for Chronic Obstructive lung disease definition of COPD (Grade II-IV). They were divided into two phenotypic groups. 1. Irreversible asthma (A and B) (n = 13): A. Asthma: Bronchial biopsy shows diffuse thickening of basement membrane (≥ 6.6 μm). B. Airflow limitation (AFL) likely to be asthma: KCO > 80% predicted if the patient refused biopsy. 2. COPD (A and B) (n = 19): A. COPD: hypercapneic respiratory failure with raised bicarbonate, panlobular emphysema with multiple bullas, or bronchial biopsy showing squamous metaplasia and epithelial/subepithelial inflammation without thickening of the basement membrane. B. AFL likely to be COPD: KCO < 80% predicted. RESULTS: The asthma phenotype was significantly younger, had a strong association with hypertrophy of nasal turbinates, and registered a significant improvement of FEV1 (350 ml) vs a decline of - 26.5 ml in the COPD phenotype following therapy with budesonide/formoterol for one year. Withdrawal of budesonide for 4 weeks in the COPD phenotype resulted in FEV1 + 1.33% (SD ± 5.71) and FVC + 1.24% (SD ± 5.32); a change of <12% in all patients. CONCLUSIONS: We recorded no spirometric deterioration after exclusion of the asthma phenotype from a COPD group.

Can computed tomography and carbon monoxide transfer coefficient diagnose an asthma-like phenotype in COPD?

Post‐mortem and computed tomography (CT) studies indicated that emphysema is a feature of COPD even in the ‘blue bloater/chronic bronchitis’ type. We aim to test the hypothesis that the non‐emphysematous patients are distinct from the main body of COPD and are more akin to asthmatic patients.

The dangers of incense burning: COPD in Saudi Arabia

We read with great pleasure the letter to the editor written by Professor Al-Kassimi and we thank him for his interest in our paper “Chronic obstructive pulmonary disease: hospital and intensive care unit outcomes in the Kingdom of Saudi Arabia.”1 Our response to the queries raised by the comments 1 and 3 are shown below; comment 2 was simply the reiteration of limitations noted by ourselves in the discussion section of our paper. We agree with his concern that several forms of environmental smoke exposure may contribute towards COPD and this should have been better acknowledged in the discussion section of our paper. While we agree that smoking is one of the most studied COPD risk factors, the possibility of non-smokers developing this illness is not unheard of, as shown in epidemiological studies on this matter.2,3 In our opinion, classifying non-smokers as asthmatics in our study may not be an accurate representation of our patients. We acknowledge the concern raised by Professor Al Kassimi related to the mortality rates in our study being low secondary to inclusion of non-smokers who may not have had COPD to start with. Accordingly, in our study we have analyzed the results of smokers and non-smokers separately, as shown in Table 1. It is important to note that there were no statistically significant differences observed between smokers and non-smokers with regards to ICU or overall mortality. Therefore, we may conclude that the inclusion of non-smokers is unlikely to be the reason for lower mortality rates seen in our study. Table 1 The outcome of COPD patients admitted to the ICU

Re: Phenotyping of chronic obstructive pulmonary disease: heterogeneity and its clinical relevance

We read the above article (published in Curr Respir Care Rep 2012 1:189–198) with great interest, and would like to make the following comments. The review very correctly refers to the great potential of targeting therapy to specific COPD phenotypes, and indeed cites several valuable examples of targeted therapy. However, there is no mention of the two most important of these phenotypes, namely irreversible asthma and eosinophilic COPD. Approximately 35 % of COPD patients suffer from irreversible asthma, as evidenced by bronchial histology, normal carbon monoxide diffusion capacity, absence of emphysema on CT scan, strong association with allergic rhinitis, and responsiveness to prednisolone or inhaled corticosteroids (ICS) [1–3]. Eosinophilic COPD, defined by sputum eosinophilia of more than 3 %, is reported for 20– 40 % of COPD patients. Apart from these two phenotypes, cases of COPD are not steroid-responsive [4–7]. Identifying these two groups would result in more effective and less expensive therapy. The review defined the “overlap syndrome” (of asthma and COPD) as the presence of increased variability of airflow in a COPD patient. There is no agreement on a definition of the “syndrome” because workers have used a variety of other criteria to diagnose it, including the patient reporting having received an asthma diagnosis (with or without age limitation) [8], or the presence of “asthmatic symptoms” including cough, episodic chest tightness or wheezing in a patient with COPD [9, 10]. Sputum eosinophilia or atopy have also been used as criteria for diagnosis [11, 12]. In therapeutic trials the response of the “overlap syndrome” to ICS was not uniform, but was related to the presence of sputum eosinophila [9]. This further demonstrates the heterogeneity of the “overlap syndrome” and the difficulty of accepting its existence as a distinct, definable entity or phenotype. The condition has been called a “nonsyndrome” because of its arbitrary definitions on which there is no agreement, its inability to be defined by objective criteria, for example histology or CT scan, and its lack of uniform response to ICS [13]. More seriously, accepting the existence of an overlap syndrome could adversely affect phenotyping and its objective of separating the different strands of COPD.

The perils of laboratory research

Pneumatoceles are acquired air cysts that develop after lung infection, pulmonary trauma (laceration), or hydrocarbon ingestion. They represent an area of localized pulmonary over inflation caused by transient bronchial or bronchiolar obstruction of the check-valve type.[4] The obstruction is believed to be caused by inflammatory exudates within the airway lumen or wall, allowing air to enter the cystic space but not to leave it. Pulmonary pneumatoceles are formed initially by drainage of necrotic lung parenchyma and subsequent enlargement of the pneumatocele caused by check-valve bronchiolar obstruction, which is due to either pressure from the adjacent pneumatocele or intraluminal inflammatory exudates. Pneumatoceles are generally observed soon after the development of pneumonia but can be observed on the initial chest radiograph. Radiographic evidence of a pneumatocele most often occurs on day 5–7 of hospitalization. They can be single but are more often multiple, thin-walled, air-filled, cystlike cavities, or “ring shadows” greater than 1 cm in diameter with wall <4 mm and of uniform thickness.[5] No specific genetic factor is known to predispose individuals to pneumatocele formation. However, pneumatoceles are associated with hyperimmunoglobulinemia E syndrome (Buckley–Job syndrome), which predisposes the patient to staphylococcal pneumonia. Other organisms that may lead to this condition include Streptococcus pneumoniae, Haemophilus influenzae, E. coli, S. pyogenes, Serratia marcescens, K. pneumoniae, adenovirus, M. tuberculosis, and Pneumocystis jiroveci. Trauma and hydrocarbon ingestion may also play a role. Pneumocysti carinii is also a well-recognized cause of pneumatocele formation in adults. Even though E. coli pneumonia might be a common cause of pneumatocele in children, our Medline research has identified only one such case in adult patients.[6]