induced sputuM in hiv-infected patients : diagnOsis Of acute pulMOnaRy diseases

Rev Assoc Med Bras 2009; 55(5): 617-20 *Correspondência: Serviço de Clínica Médica do Hospital do Andaraí Av. Maracanã, 1.481 apto. 401 Rio de Janeiro – RJ 20511-000 gers-rio@yahoogroups.com Summary Objective. To make a narrative review of the accuracy of induced sputum for diagnosis of pulmonary disease in HIV-infected patients. Data sources: The MEDLINE, LILACS, EMBASE and the Cochrane Library were searched. reference lists, abstracts of conference proceedings and scientific meetings were hand searched. MethOds. Study selection: Fifteen articles that specifically addressed the stated purpose were selected. Data extraction: Yield of sputum induction and fiberoptic bronchoscopy with bronchoalveolar lavage were analyzed using explicit methodologic to evaluate the quality of clinical trials. Results. Sputum induction demonstrated 55.5% sensitivity and 98.6% specificity to Pneumocystis pneumonia. Sensitivity of sputum induction was significantly higher with immunofluorescence than with cytochemical staining (67.1 versus 43.1%). Sputum induction for diagnosis of bacterial pneumonia demonstrated 60% sensitivity, 40% specificity, 80% positive predictive value, 20% negative predictive value and 56% accuracy. In relation to tuberculosis, sputum induction demonstrated 36% sensitivity, 100% specificity, 100% positive predictive value and 54.2% negative predictive value. cOnclusiOn. Sputum induction seems to be effective and safe for diagnosis of pulmonary diseases in HIV-infected patients.


backgROund
The spectrum of pulmonary manifestations in patients infected with human immunodeficiency virus (HIV) is broad, including many infectious and noninfectious complications.In the evaluation of an HIV-infected patient with diffuse pulmonary disease, a definitive diagnosis is preferred over empiric therapy in most patients.Patients, usually receive empiric treatment for community-acquired pneumonia or pneumocystosis, with nonresponders undergoing additional diagnostic testing 1 .
Pneumonia is the leading HIV-associated infection.It is estimated that 65% of the patients infected with HIV will present pulmonary involvement as their first clinical manifestation of the syndrome and that approximately 80% of these patients will present some kind of pulmonary involvement in the course of the disease 2 .
The spectrum of microorganisms includes bacteria, mainly Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Mycobacterium tuberculosis.In addition, fungi such as Pneumocystis jiroveci, Cryptococcus neoformans and Histoplasma capsulatum are common HIV-associated pathogens.Diagnostic work-up relies on the epidemiology and immune status (CD4-lymphocytes count).Imaging techniques are always required, and the microbiological analysis of expectorations should be performed 3 .

Induced sputum in HIV-infected patients
In 1958,a simple, harmless and efficient method for artificial induction of sputum was described.It was first considered as a potentially useful method for early detection of lung cancer 4 .
This technique was logically extended to patients with pneumonia who had a nonproductive cough.In 1964, a study reported an experience applying this method to 15 patients with pneumonia who were unable to produce sputum voluntarily.In 13 (87%) of these cases, a bacteriologic diagnosis was reported 5 .
In the mid-1980's the examination of induced sputum by inhalation of hypertonic saline solution was frequently used to diagnose pneumocystosis (PCP) in patients with acquired immunodeficiency syndrome 6 .
Since then, this technique has emerged as a simple and noninvasive procedure, although a rather wide variation in diagnostic accuracy has been reported.
While induced sputum may be less invasive and less expensive to perform than bronchoscopy, cost is not trivial, and has been reported to be approximately 40% the cost of bronchoscopy 7 .
Although sputum induction appears to be a safe and relatively simple method, it is important that the staff involved at all stages of this test be properly trained 8 .

Induced sputum in HIV-infected patients Purpose
To make a narrative review, for clinicians and pneumologists, about the accuracy of sputum induction for diagnosis of pulmonary disease in HIV-infected patients.

Induced sputum in HIV-infected patients Study selection
Several articles were independently selected and reviewed by two reviewers.Disagreement was resolved by consensus with a third party.Only studies that evaluated the yield of induced sputum in diagnosis of pulmonary disease in HIV-infected patients were included.

Induced sputum in HIV-infected patients
Sputum induction has proven useful in the diagnosis of Pneumocystis jiroveci pneumonia and mycobacterial infections, but data are scant on its use for diagnosis of community-acquired pneumonia (CAP).There was no significant difference in the sensitivity of induced and expectorated sputum for diagnosis of PCP when the direct fluorescent antibody method of staining was used 7 .When BAL was the gold standard, sputum induction in PCP demonstrated 55.5% sensitivity and 98.6% specificity.Sensitivity of sputum induction was significantly higher with immunofluorescence than with cytochemical staining (67.1 versus 43.1%).In settings of 25-60% prevalence of PCP, positive and negative predictive values ranged 86-96.7 and 66.2-89.8,respectively, with immunofluorescence, and 79-94.4 and 53-83.5% with cytochemical staining 16 .
In sputum induction for diagnosis of bacterial pneumonia, sensitivity was 60% and specificity 40%; the positive predictive value (PPV) was 80%, negative predictive value (NPV) 20% and accuracy 56%.In addition, sputum induction with quantitative culture can be helpful for diagnosis of bacterial pneumonia in HIV-positive patients 14 .
Among tuberculosis HIV-seropositive patients, agreement between acid-fastbacilli (AFB) smear and culture results for sputum induction and BAL specimens were 98% and 86%, respectively.The PPV of an AFB smear for diagnosis of pulmonary tuberculosis (PTB) was 100% and NPV 54.2% among seropositive patients undergoing sputum induction or BAL 9 .In a setting with a high prevalence of Mycobacterium avium complex in respiratory specimens, the predictive value of the acid-fast bacilli smear for Mycobacterium tuberculosis was 92% for expectorated sputum specimens, 71% for sputum induction specimens, and 71% for BAL specimens 21 .

Induced sputum in HIV-infected patients
These findings reflect the different prevalence of isolation of mycobacteria other than those of tuberculosis in respiratory specimens.
Sputum induction by hypertonic saline inhalation does not improve specimen quality as indicated by the PMNs (polymorphonuclear neutrophils) / SECs (squamous epithelial cells) ratio on Gram stain 22 .

discussiOn
We found that sputum induction is a sensitivity and specificity test to detect pulmonary disease in HIV-infected adult patients.There are several benefits of sputum induction when compared to BAL.This technique is less expensive and invasive than bronchoscopy with BAL, saves time, and is painless.Attempting induction early, preferably before starting antibiotics, may increase its diagnostic yield.Bronchoscopy is an invasive procedure and is not easily applicable on a large scale.

Induced sputum in HIV-infected patients
In PCP, sputum induction has a significant higher sensitivity with immunofluorescence staining when compared to cytochemical staining of sputum specimens 16 .Moreover, the decreased prevalence of PCP related to widespread use of antibiotic prophylaxis, and availability of highly active antiretroviral therapy (HAART) provide further grounds for re-evaluation of Pneumocystis jiroveci diagnosis 16 .
Pulmonary tuberculosis (TB) remains one of the most important health problems in the world.Nearly 2 billion people -about one third of the world's population -are infected with tuberculosis

Patients with respiratory tract infection productive cough
Patients were in the induced (n = 58) and spontaneous (n = 62) sputum groups.Quality was assessed by evaluating the ratio between polymorphonuclear neutrophils and squamous epithelial cells on Gram-stained specimens Sputum induction by hypertonic saline inhalation does not improve specimen quality bacteria 23,24 .Each year, Nearly 9 million people develop active tuberculosis, the infectious form of the disease, every year, and 2 million people experience TB-related deaths each year 25 .
In Brazil, with an estimated annual prevalence of 129,000 new cases of TB, approximately 22% of adult patients with suspected pulmonary tuberculosis do not produce sputum spontaneously 9.Sputum induction is a safe procedure with high diagnostic yield and good agreement with results from fiberoptic bronchoscopy 9 .Thus, sputum induction is a valuable tool for diagnosing pulmonary tuberculosis.
Use of HAART in a region with a high incidence of TB may reduce the risk of this disease among HIV-infected patients.The use of HAART was associated with an 81% reduction in risk of TB 26 .Free access to HAART may contribute to reduce the incidence of TB in populations with a low socioeconomic level and high prevalence of coinfection with HIV and M. tuberculosis 26 .

Induced sputum in HIV-infected patients
Although a reduction in the risk of tuberculosis was not initially apparent, recent reports from large observational studies performed in Europe, have suggested that antiretroviral therapy has a protective effect 27 .If the prevalence of TB with HAART is reduced, we do not know whethetr sputum induction would have the same diagnostic accuracy.
Patients who underwent sputum induction experienced side effects in a way similar to patients who had bronchoscopy with BAL 9 .It is recommended that sputum be processed as soon as possible or within two hours, in order to ensure optimum cell Artigo recebido: 07/07/08 Aceito para publicação: 07/03/09 counting and staining 23 .If the specimen of sputum induction is negative, then bronchoscopy with BAL should be performed.Transbronchoscopic surgical lung biopsy is seldom needed.cOnclusiOn Sputum induction is effective to obtain sputum in HIV-infected patients who fail to expectorate.For these patients sputum induction may be a technique that is safe and easily performed, with a good diagnostic yield.

acknOwlwdgMents
We thank Sonia M. R. Vasconcelos (UFRJ) for the critical review of this manuscript.