COlOlOuoalilol II • • • CommunlctJflonl for thu aection will be publUhed tJ8 IptJCB and prfofitia permU. 'l7ae commIJntI .Iaould not exceed 350 wonla in l.ngth, with tJ mafmum offioe ,.qermce,; onefigure or table can be prim.d. ErcqfIoru mtJfI occur under parlicular drcumatanca. ConIribuflona may iraclu* commenu on arlicla publUh8d in this ".nodIt;tJl, or they mtJfI bereport» ofunique educational character. Specfjic ".",....,. to publUh .Iaould be cited in a covering letter or ~
tJI tJ
pomeript.
Ina M. Gilmore, M.D.; Carol]. Camp, M.S.; FredMic1c B. Roae, M.D.; tJnd RobertJ. Lenox, M.D.,
D.,,1mentl ofInfectiotu IJiIeGN" Patlaololfland Pulm0n4'l1 Medicine, Guthrie Medkal Cm~ StJyre, PA
Reprint requaf8: Dr. Roae, Guthrie M«lIctJl Cmter, Sayre, PenMflIvania 18890
REFERENCES
1 Lake ICB, Browne PM, Van Dyke JJ, Ayers L. Fatal disseminated
F8ta1 Pulmonary Aspergillosis following a Farm Accident
2
To tIN Editor:
3
We read with interest the recent report by Lake and assoeietes'
that short-coune corticosteroid therapy may be the only risk factor fOr developing diueminated aspergillosis. We recently cared for a previously healthy immunocompetent man with no known lung disease who developed fatal pulmonary aspergillosis after a twoweek course of corticosteroids. Unique to this case was antecedent trauma involving farm equipment. CASE REPORT
A 70-year-old farmer caught his right sleeve in the drive shaft of a manure spreader, trapping him against the machine for 15 minutes. This incident occurred on December 12, 1982. He was hospitalized for three days, for treatment of a bnchia1 plexus injury with dexamethasone [Decadron] 6 mg qid. Over the next two weeks, the Decadron was tapered to 1 mg tid. A chest radiograph on December 12showed normal Bndings. On December 31,he was re-hospitalized fOr treatment of a tbree-day bout of chest pain and cough. White blood cell count (WBC) was 20,1500 with fr1 percent neutrophils. Amibcin and ticarcillin were started. Sputum cultures showed PIflUdomontu~. On tranJfer to our hospital on January 6, the WBC count was 6,900 with 94 percent neutrophils. Chest radiograph showed bilateral 8ufFy infiltrates with bilateral nodulation, some of which were cavitated with CocaI consolidation in the right upper lobe, lingula, and right lower lobe. Antibiotics and corticosteroids were discontinued upon tranJfer. Fiberoptic bronchoscopy with biopsy of the right upper lobe revealed hyphae consistent with Aspergillus within aIveolt and in necrotic tissue. Pathologic findings were not consistent with bacterial pneumonia. AapergillfU fumigaltu was cultured from bronchial brushings. Despite amphotericin B therapy, the patient expired 24 days later secondary to respiratory insufticiency. A post-mortem examination was not pemrmed.
A.".,.alfU fumigtJlul is an indigenous inhabitant of compost and 81 a thermophile, grows well in manure. I Although conlroveny exists concerning occupational predisposition to aspergillosis,:1.4 we postulate that the prolonged entrapment in the manure spreader exposed our patient to a large inoculum of A~ conidia and was the initiating ~nt in the development of disease. Subsequent corticosteroid therapy rendered him immunoincompetent and resulted in overwhelming invasiw disease. We would suggest an addendum to the editorial comments" that a diqnosis of invasive aspergillosis be considered not only as a consequence of acquired immunodeficiency syndrome, but also in the farm worker who presents with an unusual pulmonary inBltrate and history of prolonged exposure to manure.
4 5
aspergillosis in an asthmatic patient treated with corticosteroids. Chest 1983; 83:138-39 Bennett JE. Aspergillus species. In: Mandell GL, et al, eds, Principles and practices of infectious diseases. New York: John Wtley ~ Sons, 1979: 2002 Macartney IN. Pulmonary aspergillosis: a review and description of three new cases. Thorax 1964; 19:287 Hertzog AJ, Smith TS, Gobin M. Acute pulmonary aspergillosis: report of a case. Pediatrics 1949; 4:331-35 Strieder DJ: Aspergillosis: old facts, new facts and speculations (editorial). Chest 1983; 83:4-5
7b th8 Editor: The recent editorial by Dr. Strieder (Ch8.1983; 83:4-5) may be
misleading. The author suggests that invasive aspergillosis may be seen with increasing frequency in young adults with acquired immunologic abnormalities inwlving the T-cell. Whilean increased number of other types of fimgal infections may occur when the cellmediated immune system is altered, this is probably not applicable
to Aspergillus infection. In fact, it is not the T-cea as Dr. Strieder asserts, but the neutrophil (or monocyte) which is primarily responsible i»r normal host defense against Aspergillus species. 1 Invasive aspergillosis is 20 times more frequent in acute leukemia than in lymphoma or transplant patients, the latter maladies involving T-cell dysfunction. I Cohen et aPhavedemonstrated that patients with chronic granulomatous diseue who have normal immunoglobulins and intact cell-mediated immunity haw pulmonary and osseous aspergillosis as their most common fungal infection. These patients have a neutrophil defect in generation of superoxide-free radicals which inhibits microbial Idlling once the organism is phagocytized. FurtbeJ; it is recognized that the risk of invasive aspergillosis may be the greatest in neutropenic patients, 4 and their survival is most enhanced by I'fNenalof this neutropenia alongwith inducing remission of the underlying disease. 5 Thus, it is not surprising that to date invasive aspergillosis is not commonly associated with the acquired immunedeftciency syndrome' which most often afIects homosexuals, Haitians, drug addicts, and hemo-
philiacs.
John W Peten, M.D.; tlnd G. WfllitmaAWuon, M.D., EC.C.l, ClUe/, PulmontJrv Section, Prubr/terllJn-U,..,...", ojPmMfl'VtJnia M«lIctJl Cmter, PlaIltuWpIaiG
REFERENCES 1 Atkinson G~ Israel H. Aspergillus. In: Fishman ~ eel. Update: pulmonary diseasesand diaorden. New York: McGraw-Hill, 1982 2 Levine AS, SchimpfF SC, Craw RC, YouDg RC. Hematologic malignancies and other marrow failure states: progress in the management of complicating infections. Semin Hematol 1974; 11:141 3 Cohen MS, Isturiz RE, Malech HC, et aI. Fungal infection in
chronic granulomatous disease: the importance of the phagocyte in defense against fungi. Am J Moo 1981;71:59-66 4 Aisner J, Schimpff SC, Wiernik PH. 'Ireatment of invasive aspergillosis: relation of early diagnosis and treatment to response. Ann Intern Med 1977; 86:539-43 5 Herbert PA, Bayer AS. Fungal pneumonia (part 4): invasive pulmonary aspergillosis. Chest 1981; 80:220-25 6 Durack 01: Opportunistic infections and Kaposis sarcoma in homosexual men (editorial). N Engl J Med 1981; 305:1465-67
To the Editor: In presuming to comment on the recent article by K. B. Lake et al (Chest 1983; 83:138-39), I chose to consider the particular circumstances of asthmatic patients stricken with pneumonia and respiratory failure, and the pronounced effects of corticosteroids on T-cell function. Dr. Gilmore and collaborators, and Drs. Peters and Atkinson remind us that there are many other epidemiologic and immunologic aspects of Aspergillus infections, for which I thank them. As to the likelihood of invasive aspergillosis affecting patients with the acquired immunodeficiency syndrome, Dr. Peters may well be right-time will tell.
Denise]. Strieder; M.D., Associate Professor ofPediatrics Massachwetts General Hospital, Boston
Nitroglycerin Therapy of Asthma To the Editor: A 12-year-old steroid-dependent asthmatic boy with iatrogenic Cushings disease, was receiving theophylline sufficient to produce therapeutic blood levels. He was also taking metaproterenol orally, as well as inhaled albuterol, beclomethasone and ipratropium bromide, an investigational atropine derivative. His dosage of prednisone ranged between 50 and 100 mg per day. Sodium cromolyn had been ineffective when given prophylactically in a relatively asymptomatic period. Short-term inhaled albuterol did not improve results of pulmonary function tests. It was decided to try the nonspecific smooth muscle dilator, nitroglycerin, continuing all other medications at their previous dosages. Prior to administration of0.15 mg of nitroglycerin sublingually, the FEVI was 1.54 (54% of predicted) and the patient was in moderate respiratory distress. Five minutes later the FEV1 was 2.11 (74% of predicted) and the patient was symptomatically improved. He is now using a 10 cm l transdermal patch containing 25 mg of nitroglycerin daily with minimum side effects (very mild intermittent dizziness), and has tapered his steroid dosage to nothing. There has been no orthostatic hypotension. Follow-up has been three months. It would appear that nitroglycerin dilates bronchiolar smooth muscle by a mechanism unrelated to that usually affected by current bronchodilating medications. The patients spirometric results were not altered by inhaled albuterol, indicating maximal adrenergic effect and probable nonresponsiveness to parenteral epinephrine. 1 Although there is little information on its use in pediatric patients, the literature gives conJlicting reports about the efficacy of nitroglycerin in acute asthma.1,3 I was unable to discover any reports of long-term therapy. It seems that nitroglycerin may have therapeutic benefit when given on a long-term basis, as well as short-term, although tachyphylaxis to its antianginal effects is known to occur in adult patients. The mode of action of nitroglycerin on bronchiolar smooth muscle can only be speculated upon. It is known to relax tracheal smooth muscle when given intravenously" Nebulized isosorbide dinitrate, a related drug, was found to be effective in seven patients aged 14-49
with extrinsic and reproducible exercise-induced asthma. 5 This compound has been found to produce vasodilation in the endothelium of coronary artery smooth muscle by the reproduction of nitric oxide which stimulates guanylate cyclase, producing cyclic GM~e
Nitroglycerin has also been shown to stimulate production of prostacyclin in human endothelial cells, thereby stimulating adenyl cyclase." It has been suggested' that this enhancement may be caused by inhibition of thromboxane Atsynthesis, thereby preferentially shunting precursor into the prostacyclin synthetase pathway. Caution should be used when prescribing nitroglycerin for the hypovolemic patient, since it may produce hypotension, an effect which may even occur in the normovolemic patient Nitroglycerin treatment of pediatric asthma is worthy of further trials and may be indicated in selected patients.
Jay A Goldstein, M.D. Anaheim Hills, California Rep1:int requests: Dr. Goldstein, 500 South Anaheim Hills Rood, Aooheim, California 92807 REFERENCES 1 Becker AD, Nelson NA, Simons FER. Inhaled salbutamol 2
3
4 5
6
7
8
(albuterol) vs injected epinephrine in the treatment of acute asthma in children. J Pediatr 1983; 102:465-69 Kennedy 1: Summer WR, Sylvester }, Robertson D. AiJway response to sublingual nitroglycerin in acute asthma. JAMA 1981; 246:145-47 NTG safe for patients with bronchospasm: Mod Med, 1983; 61 Byrick 8J, Hobbs EG, Martineau R, Noble WHo Nitroglycerin relaxes large airways. Anesth Analg 1983; 62:421-25 Tullett WM, Patel KR. Isosorbide dinitrate and isomprine in exercise induced asthma. Br Med J 1983; 286:1934-35 Galves PE, DiSalvo J. Concentration and time-dependent relationships between isosorbide dinitrate-induced relaxation and formation of cyclic GMP in coronary arterial smooth muscle. J Pharm Exp Ther 1983; 224:373-78 Levin RI, Jaffe EA, Weksler BB, Tack-Goldman N. Nitroglycerin stimulates synthesis of prostacyclin by cultured human endothelial cells. J Clio Invest 1981; 67:762-69 Zelis R. Mechanisms of vasodilation. Am J Med 1983; 74:3-12
Noninvasive Measurement of Mixed venous PC02 To the Editor: We would like to comment on the report on mixed venous Pco, in the article "Non-invasive monitoring of arterial blood gases: a report of the ACCP Section on Respiratory Pathophysiology" (Chest 1983; 83:666-70). We have been using the equilibrium rebreathing technique for measurement of mixed venous Pco, (NCO.) in patients for many years and have published several articles designed to help the physician understand and use this technique. We feel, however, that Drs. Burki and Albert's description of the two rebreathing techniques for measurement of PYCO. may confuse the reader, and also contains some inaccuracies. Two methods of estimating the PYC01 by rebreathing are in common clinical use. The Campbell and Howell technique' is a twostage procedure, in which the patient breathes for !VI minutes from a bag containing pure oxygen, breathes air for 2 min, then rebreathes from the bag for 20 sec. The PYCO.is the Pco, in the bagat the end of the second period of rebreathing. The choice and latitude of these times and volumes are explained in a later paper. I This two-stage method has the advantage of not requiring a rapidly responding analyzer, but it does require constant practice. We find it quite satisfactory when performed by trained technicians and use it in the general wards and clinic. CHEST I 85 I 3 I MARCH. 1984
449