AeroBid Inhalers

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Communications for this section will be published as space and priorities permit. The comments should not exceed 350 words in length, with a maximum offive references; onefigure or table can be printed. Exceptions may occur under particular circumstances. Contributions may include comments on articles published in this periodical, or they may be reports of unique educationalcharacter. Specificpermissionto publish should be cited in a covering letter or appended as a postscript.

Virulent Course of Bacterial Pneumonia

In a Male Homosexual

To the Editor: We have read with interest the case reports by White and associates on "Life-Threatening Bacterial Pneumonia in Male Homosexuals with Laboratory Findings of A.I.D.S."'l We would like to report yet another case with features that are very similar to Dr. White's case. Our patient was a 32-year-old male homosexual who was admitted to Hahnemann University Hospital in September, 1981with severe right-sided abdominal pain, nausea and vomiting. His past medical history was completely negative except for chronic active hepatitis treated in another state. Chest x-ray examination on admission demonstrated a small patchy infiltrate in the right lower lobe. The patient's mental status was clear and there was no evidence of aspiration. U.G.I. test results were negative, with no evidence of esophageal perforation. Soon after admission, the patient began to spike high fevers and complain of severe bilateral pleuritic chest pain. Blood cultures were positive for small gram-negative rods, which subsequently grew out Hemophilusinfluenzae. Within 48 hrs of admission, his pulmonary status began to markedly deteriorate. His chest x-ray film evolved bilateral Infiltrates associated with large bilateral effusions. Bilateral chest tubes were placed and approximately 1.5 L of pus drained from each hemithorax. The drainage from both chest tubes grew out H flu A laparotomy was performed and results were unremarkable. The patient was started on therapy with ampicillin, 2 g I.v. every four hours. Four days after admission, chest x-ray film showed a widening in the cardiac silhouette. A bedside echocardiographic examination showed a large pericardia! effusion. A sub-xiphoid pericardial tube was placed, which drained 250 ml of pus also containing Hflu. The patient continued to have a stormy course and was switched to therapy with intravenous choloramphenicol. A repeat echocardiographic examination showed reaccumulation of pericardial ftuid despite the pericardia! drain. Chest x-ray films also revealed worsening of pleural effusions despite chest tubes draining in good position. Post-operatively, the patient continued to reaccumulate pleural and pericardial fluid. He remained febrile and extremely toxic. He wastaken back to surgery 24 hrs after the pericardial tube placement for a pericardectomy, bilateral decrotication and drainage of mediastinal pus. The patient improved for a brief period of time; however, a repeat cr scan showed more pleural and pericardial collection. The patient returned to surgery yet another time for more drainage of pus. This time, he became afebrile post-operatively and subsequently began to recover despite a superinfection of the pleural space with enterococcus. The patient exhibited absence of delayed skin test reactivity throughout the hospitalization, and lymphopenia was also present throughout. After a prolonged and stormy hospital course, the patient finally recovered

and was sent home. His total hospital time was over 10 wks. He was followed and remained well for approximately one year following these events and was then lost to follow-up. The identification of helper/suppressor T-cell subsets was unavailable at our institution at that time. DISCUSSION

Hemophilus influenzae is a gram-negative organism which is classically seen to cause a wide spectrum of disease in the pediatric age group. While thought to be less common in adults, the literature reports numerous cases of H flu infections in adults of all ages. These patients are typically middle-aged and older and have some type of associated medical disorders. The patient we have just reported developed an overwhelming virulent course with Hemophilus injluenzae, which would be very uncommon in a previously healthy 32-year-old man. The combination of mediastinitis, pericarditis and bilateral empyema is very rare as a complication of pneumonia in any patient population. There was no evidence that these complications arose from esophageal rupture. We agree with Dr. White that bacterial infections may be important in the immune status of the homosexual population. The clinical course of this homosexual patient certainly is not typical and further understanding of the immune status of these individuals is certainly warranted, especially involving their B-cell function. Robert A Promislojf, D. 0., F. C. c.e. Gregory S. Lenchner, M.D., F.C.C.l, Dicision of PulmonaryDiseases, Hahnemann University, Philadelphia REFERENCE

1 Stover DE, White DA, Romano PA, Gellene RA, Robeson WA. Spectrum of pulmonary disease associated with acquired immune deficiency syndrome. Am J Med 1985; 78:429-37

AeroBld Inhalers To the Editor: In January 1985, Key Pharmaceuticals supplied five AeroBid (flunisolide) inhaler systems. While demonstrating these units to patients, it became apparent that using the device as specified in the manufacturers instructions did not release one dose of medication, despite multiple depressions of the cartridge. A series of tests (1able 1) were performed to compare the AeroBid inhaler system to the Beclovent (beclomethasone, Glaxo) inhaler and the Azmacort (triamcinolone acetonide, Rorer) inhaler.

Table I-Number ojDepreaionB Needed to Deliver Metered Doae Inhaler Medication Number of depressions

AeroBid Beclovent Azmacort

1

2

3

1 3

2

1

2

1

4

5

6 1

4

CHEST I 88 I 6 I DECEMBER, 1985

Total Units Tested

5 5 5

935

Although the sample is limited, it is impressive that two of the five AeroBid inhalers required more than three depressions of the cannister to activate the metered dose system and one of the five tests required six depressions prior to activation of the aerosol. None of the other inhaler systems tested required more than two depressions to activate the inhaler. The devices were again tested threedays later and all systems were activated by two or fewer depressions. The package insert does not indicate that such variable response to depressions can be expected. Since physicians often prescribe metered dose inhaler systems that are dispensed by pharmacists, they may not be aware of the frequency with which these devices do not release medication. The proliferation of spacing devices which currently are being promoted fur use with metered dose inhalers underscores the problems with effective aerosol delivery. U.3 We suggest that the patient be warned that, during the initial use of the inhaler, release of medication may not occur and perhaps the inhaler should be discharged against background light when first used to insure that delivery of the medication is, in fact, occurring.

Bernhard A Votteri, M.D., F.C.C.P.; and

Cindy BUrl, R.N ., M.S ., Sequoia Hospital District, Redwood City, California REFERENCES 1 Shim C, Williams MH . The adequacy of inhalation of aerosol from cannister nebulizers. Am J Med 1984; 69:891-94 2 Sell TH, Brooks JB. Necessity of teaching patients correct bronchodilator inhalation technique. Immun Allergy Pract 1983; 4:27-31 3 Epstein SW, Parsons JE, Covey PN, Worsely GH , Reilly PA. A comparison of threemeans of pressurized aerosol inhaler use . Am Rev Respir Dis 1983; 128:253-55

Combination of Flow Cytometry and 'lransbronchlal Needle Aspiration In the Diagnosis of Mediastinal Lymphoma To the Editor: Mediastinal adenopathy is the most common manifestation of intrathoracic lymphoma. 1 Halfof patients with Hodgkins disease and approximately 20 percent with non-Hodgkins lymphoma (NHL) will demonstrate mediastinal adenopathy at the time of diagnosis .I This may recur with relapse of the disease. Poorly differentiated lymphocytic lymphoma (PDLL), the most frequent type ofNHL to be found intrathoracically, commonly relapses fullowing chemotherapy," We have used the combination of transbronchial needle lymph node

aspiration and Bowcytometry to identify recurrence ofPDLL in the mediastinum. A 58-yellNlld man was diagnosed as having stage 4 PDLL in 1971. Treatment with cyclophosphamide, vincristine, and prednisone produced a complete response. Maintenance cyclophosphamide therapy was continued until 1979, and the patient remained in remission. In October, 1984 a routine chest roentgenographic examination revealed a new hilar abnormality. A repeat roentgenographic examination in March , 1985 -demonstrated increased size of the mass, and the patient was admitted fur evaluation. Physical exam showed no abnormality. Peripheral blood count and bone marrow biopsy results were normal. Chest computerized tomographic study confirmed the presence of a right hilar mass. It also revealed a 3 X 1 em right paratracheal (RPT) node, a 1.5 cm subcarinal (SC) node, and a 1.5 em aortopulmonary window node (Fig 1). At fiberoptic bronchoscopic examination, there were no endobronchial lesions . Under fluoroscopic guidance, transbronchial needle aspiration was performed of both SC and RYf nodes. Aspirated material was sent fur routine cytologic and Bow cytometric study. With Bow cytometric examination, the aspirated cells were separated into subpopulations on the basis of light scatter characteristics. Cells were stained with a panel of monoclonal antibodies, and percentages of each marker reported fur the "lymphoid" subpopulations . Simultaneous analysis of DNA content was performed, Papanicolaou preparations of both RPT and SC nodes were interpreted as showing mature lymphocytes. Flow cytometric analysis revealed the presence of two populations of cells as assessed by light scatter. The population of larger cells was predominantly B-cell in origin (81percent positive fur Bl, a B-cell surface marker). Only 16 percent of the cells were positive fur TIl, a pan-T cell marker. The T4I T8 (helper/suppressor) ratio was 1:8. Technical difficulties limited the detection of surface immunoglobulin. No aneuploidy was present. Flow cytometric findings were consistent with a B-celllymphoproliferative disorder; Ie, recurrence of the patient's PDLL. Biopsy material from subsequent mediastinoscopic study revealed reactive lymphadenopathy interspersed with nodular PDLL, positive fur lambda light chains. The differentiation of NHL from benign lymphocytic proliferations can be difficult by routine cytologic means alone . Flow cytometric study is an important adjunct.' PDLL, like most NHLs, represents a B-cell proliferation. B-cell predominance within a lymph node may be detected by flow cytometry and contrasts sharply with the T-cell predominance seen in normal or reactive nodes. In many cases, demonstration of monoclonal surface light chains or DNA aneuploidy may add support to the diagnosis of a B-cell neoplasm ." Flow cytometric analysis , combined with transbronchial needle aspiration, may be useful in documenting the mediastinal recurrence of a previously phenotyped NHL, perhaps obviating further surgical diagnostic procedures.

L. Ketal, M.D.;}. Chauncey, M.D.; R. Duque, M.D., University ofMichigan Medical Center, Ann Arbor REFERENCES

FIGURE 1. Computed tomographic view demonstrating right paratracheal and aortopulmonary window adenopathy.

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1 Bragg DG. The clinical, pathologic and radiographic spectrum of the intrathoracic lymphomas. Invest Radioll978; 13:1-11 2 Jenkins PF, Ward MJ, Davis P, Fletcher J. Non-Hodgkins lymphoma, chronic lymphatic leukaemia and the lung. Br J Dis Chest 1981; 75:22-29 3 Balikian JP, Herman PG . Non-Hodgkin lymphoma of the lungs . Radiology 1979; 132:569-76 4 Lovett EJ, Schnitzer B, Keren DF, Flint A, Hudson JL, McClatchey KD. Application of flow cytometry to diagnostic pathology. Lab Invest 1984; 50:115-40 5 Braylan RC, Benson NA, Nourse VA. Cellular DNA of human neoplastic B-cells measured by flow cytometry. Cancer Res 1984; 44:5010-5016 Communlcalionll to \he Editor