336 CALIFORNIA AND WZESTERN MEDICINE Vol. XXXI, No. S

VACCINE THERAPY IN INFECTIOUS 1-5 6-10 11-15 A-2021-2 26-30 31-35 3640 44-45 46+ BRONCHITIS AND ASTHMA* 5 + F I__ _ F H7H± T T I 4, ,f " ;g4r;l' By WILLIAM C. VOORSANGER, M. D. 40~~~~~J AND FRED FIRESTONE, M. D. San Francisco DIscussIoN by Albert H. Rowe, M. D., Oakland; George Piness, M. D., Los Angeles. TN two previous papers' the authors attempted 2U to classify nontuberculous cough according to its underlying pathology. Based upon a study of two hundred cases selected from routine clinic 15~~~~~~~~~~~~~~~~~1 and private practice, twenty different causes were found. The two prevailing groups, a 38 per cent "undiagnosed group," and a 37 per cent group which showed a "pulmonary infiltration and 'A~~~~I'I thickening with or without enlarged root glands." FIG. 1.-Chart showing influence of heredity on ae of onst. most often followed influenza, pneumonia, and and lactose. These serum waters were incubated occasionally pleurisy with effusion. for fourteen days unless coagulation took place PREPARATION OF VACCINE before that time. At the end of fourteen days In 1919 I. Chandler Walker22 pointed out the the tubes in which change had not taken place significance of vaccines in the treatment of bron- were carefully examined according to Holman's In his early work he recognized method of classification. Vaccines were prepared chial asthma. in the strength of one billion organisms per cubic two distinct types of asthmatic patients-those 0.05 in which some foreign protein, either of the in- centimeter, the initial dose in adults being variety, inaugurated the at- cubic centimeter, gradually increasing by 0.05 halant or ingestive cubic centimeter at a three to five to seven-day tack, and a second type in which the attack was resist- aggravated or precipitated by a superimposed interval, this time being governed by the bacterial infection. ance of the patient, as determined by local re- Since the inception of our work on infectious action and constitutional symptoms. bronchitis and asthma, we have modified some- HEREDITY AS A CAUSATIVE FACTOR what the Chandler Walker technique preparation IN ASTHMA of vaccines and of dosage, and give herewith a Cooke,4 in 1925, after a careful survey of the brief resume of our method of preparing cul- nature of the inheritance in asthma and pre- tures and vaccines including our more recent asthmatic conditions, made a graphic chart show- modifications. ing the influence of heredity Qn the age of onset. Throughout this work the following bacterio- (See Fig. 1.) logical technique was used: After thorough anti- Where both father and mother showed some sepsis of the mouth, sputum was collected daily hypersensitiveness 75 per cent of the offspring for three consecutive days in sterile sputum jars. showed clinical signs before the tenth year; where Thick masses of sputum, raised during an asth- there is a unilateral heredity, 35 per cent showed matic attack or during a severe paroxysm of symptoms before the tenth year. In the third coughing, which usually occurred in the morning, class, where there is a negative heredity his- wete washed in sterile sodium chlorid solution tory, 17 per cent showed symptoms before the and shaken in five cubic centimeters of plain tenth year. This group comprises the infectious bouillon or glucose veal broth of proper hydrogen type, and a study of the curve reveals a small ion concentration. Tubes of melted plain agar, peak rising from the first to the tenth year, a fall to which 0.5 cubic centimeters of sterile defibri- in nated human blood was added, were inoculated TABLE No. 1.-Results of Vaccines Infectious with varying amounts of the broth emulsion of Bronchitis and Asthma 2XJ3- Petri dishes and incu- i -laaIJLT sputum and poured into i;FlauM I1t"T= sm N70"9+ kI r?f ""es _Ios WJTPi bated for thirty-six hours. The various types of I--l 32 IF22 T .T-,CA.Mo..c L 2 E*Ow,m.ln3 in I1YEARSi s CHMMIC colonies were then picked off, subcultivated C2H222N 52W222ns2 PuL 2m F _ iTm1 votIDW P"OV 0 bouillon and incubated for about twenty- fALe ORONC-ITIS dextrose flfMl a3L PCOWAYC>419 :: "O WEftOL ftEPCFITED v4PROV I5 IIYEARS| W.c UTOGIENOtl5I COLOS hours. The organisms from this dextrose 222222 four - -H* M 222222m -" 2.222222|, RercATEO VN4t4P*WCD bouillon growth were stained by Gram's method 23 65 CIOLDS a bile solubility test was made. Those organ- muOCENOUS IMMUCNZA ViELL and Os If FE YEAR "M. which proved to be Gram-negative cocci in I5tH 1t ^K WVCLL *isms 2YSARS 50 lb| *E= in- RSTHg1A SC bile insoluble were &W eVlIID and m chains, noncapsulated GROW,--" .Ct mp2 GWP w4powco 12 2M22LE EraRS R oculated, according to the method of Hiss, into 3q 43 1ow".fmsyw 1-m 1 v lOce.ious P2 FIL2 Lr acpc.".. I wmp"ovco 222222a IJWOO litmus waters which contained salicin, mannite, 45 *1 ~ A P.22222222222pl - 04pnowco IE S YEARS H-: SS W -'2222222rW2 8 PUf¢C|STRP C.M OET * of Mount Zion Hospital, GRO OWUMNZFIL From the Chest Department Pfl-E 1A. V.- VIIOwo^. vS emcumoms WELL San Francisco. 62 28 |.VERPS , PUDA'kgM * Read before the General Medicine Section of the Cali- F"CL*W"I'l IMPMWO fornia Medical Association at the Fifty-eighth Annual 66 t errusom Session, May 6-9, 1929. 337 November,Novmbe,1929 129 VACCINE THERAPY-VOORSANGER AND FIRESTONE33 0 from the tenth to the fifteenth year, and a rapid trinsic asthma is the result of infectious processes. rise to the twenty-first year, where the incidence in other parts of the body, such as asthma rela'te-d of asthma stays at a maximal level until over to and relieved by removal of an' infected gall thirty years, to drop gradually to the age of forty bladder or kidney or associated with the menstrual when it climbs again, reaching its maximum at cycle. the sixty-fifth year. Asthma developing after the In our classification we demonstrated that in- thirteenth year, and especially after the fortieth, fected sinuses were responsible for 8 per cent of is usually the resuilt of chronic foci of infection all chronic coughs. We therefore emphatically in the bronchi, tonsils, teeth, and sinuses. Here, recommend in all bronchitis and asthma follow- too,-development is gradual. Cough and wheez- ing an acute upper respiratory infection that all ing and frequent attacks of bronchitis may go on sinuses be thoroughly examined, d'rained if neces- for years before the true dyspnea of asthma be- sary, and a vaccine from the sinus pus or secre- gins. Many of the cases of chronic bronchitis tion be administered. In our experience we have with emphysema are truly infectious asthma and often seen good results from the latter procedure, should early be recognized, because the results and have seldom seen permanent relief from a obtained with some of these long-standing cases purely operative correction. How often, after sub- warrant the belief that much better results could mitting the patient to trying sinus operations- be obtained had they been treated along the same either drainage or the more radical method-have lines that we now follow after they-.have become we seen a recurrence of all symptoms or a very definitely asthmatic. temporary relief. We believe frankly that many sinus infections are true secondary infections CLASSIFICATION OF CASES TREATED superimposed upon a sensitive membrane; an'd This present paper consists of a critical review we advocate the elimination of every condition of 481 cases reporting for routine chest -exami- of hypersensitiveness or allergic sensitiveness nation and includes a series of 110 cases of proved (proved such by protein skin-testing with dust, tuberculosis, as checked by physical examination, pollens, danders, and foods) by a period of rest 'c-ray films of chest, sputum, and guinea-pig in-- and vaccine therapy before surgery is employed. )culation for tubercle bacilli. These tuberculous A detailed analysis of the sixty-six cases of :ases have been eliminated from this study. Of infectious bronchitis and asthma reveals the the remaining 371 nontuberculous cases, we have following :* been able to isolate sixty-six cases of infectious Fifteen, or 22.7 per cent, we classify as "well," bronchitis and asthma which have received vac- by which we mean the patient has been clinically cine therapy, and it is this latter series that we' relieved of all evidence of the acute paroxysms report here in detail, giving our observations since of wheezing with signs of bronchospasm for a 1920. period of over two years. We avoid the term REVIEW OF SIXTY-SIX CASES OF INFECTIOUS "cured" as we feel that, in the future, repeated BRONCHITIS AND ASTHMA TREATED epidemics of influenza or other acute respiratory WITH VACCINE diseases may so alter the bacterial flora of the All patients treated had a history of some patient as to break down the resistance established acute pulmonary infection, principally influenza- and possibly precipitate an asthmatic attack. pneumonia, repeated colds, and in children whoop- Twenty-seven, or 40.9 per cent, are considered ing-cough was an underlying factor. All proved as "improved," by which we mean the patient has cases of tuberculosis have naturally been eliminated been relieved for over a period of six months of although we have in a few instances seen chronic the real asthmatic paroxysms, has lost the associ- tuberculosis, complicated with asthma, 'improve ated cough and dyspnea on exertion, and is able under an autogenous vaccine, which improvement * The table showing the results of vaccine treatment I-n we as from a tuberculin made infectious bronchitis and asthma will appear in the re- interpret resulting prints of this article, which may be had on application tco of the patients' own sputum. (See Table No. 1.) the authors. We have excluded from this study true bronchial asthma of the hereditary type and those cases due to pollen or protein sensitiza tion; in the earlier years of our work, by using the scratch method of Schloss with dried proteins, but in the last two years using the protein extracts of all the inhalants, danders, house .dust and protein antigens by the intradermal tech- nique of Coca and Cooke61 of the Cornell Clinic. 2.-Infectious brronchitis follow- Neither a reflex asthma nor iFig. d thickening of Fig. 3.-Bronchial gland involvement. are in- .bt hla with diatati,on of bronchial History of influenza with subsequent intrinsic asthma woement under bronchitis and asthma. Patient well cluded in this study. In- va Makednmer after three years. '338 CALIFORNIA AND WESTERN MEDICINE Vol. XXXI, No. S to return to his routine of living. The remaining twenty- four, or 36.4 per cent, we have considered as "un- improved," in that they still have their nightly par- oxysms of dyspnea with severe morning cough, pro- duce large quantities of a watery, frothy sputum and, clinically, present signs of bronchospasm in their chests. group of The combined Fig. 4.-Marked thiclkening of both well and improved patients hila. Thickened plebura at both Fig. 5.-Pleural thickening at left apices. Lipiodol prese nt after two base following pleurisy with effusion. comprise, in our small series years. Marked improivement under Bronchitic and asthmatic symptoms of sixty-six cases, 63.6 per vaccine. improved under vaccine. cent, and from this we con- clude that vaccine therapy affords a valuable aid and show considerable involvement of lung paren- to our armamentarium for combating the infec- chyma. tious type of bronchitis and asthma. A review A review of the cultural studies, as previ- of the cases presented will show that our results ously reported in this group of infectious asthma, have been almost directly in proportion to the age shows the prevailing organisms to be: Micro- at onset and duration of the illness, and we feel coccus catarrhalis, Streptococcus nonhemolyticus, that the earlier specific vaccine therapy is insti- Streptococcus hemolyticus alpha and beta, Strep- tuted the more beneficial results can be antici- tococcus viridans, and secondary invaders such pated. We find further that of these cases that as Gram-positive diplococci, staphylococci, and have responded so well that a recent history of pneumococci. repeated colds, sinusitis, influenza, bronchopneu- In a series of twenty-two cases where we were monia, and whooping-cough have been the chief unable to trace the onset of the asthmatic parox- etiological factors. ysms to a specific infectious process, such as in- In the group of 36.4 per cent that are "un- fluenza, pneumonia, or whooping-cough, we re- improved" we find, from our study of the physi- sorted to the use of the ordinary stock respiratory cal and x-ray findings, that the poor results are vaccine and found that our percentages of results the results of structural changes in the lung were: parenchyma such as pleural thickening, fibrosis, Well-Seven cases, or 32 per cent. basal infiltration and bronchiectasis, or an asso- or 36 per cent. ciated myocardial lesion. It is self-evident that Improved-Eight cases, all infectious bronchitis and asthma had a start Unimproved-Seven cases, or 32 per cent. perhaps with an enlarged hilus gland, perhaps These figures run parallel to our results with with peribronchial thickening, or even with mild autogenous vaccines, and are in agreement with extension into the lung parenchyma. This pathol- the work of Rackemann,8 who does not claim ogy must be discovered early if we are to effect specificity for autogenous vaccines. We are con- cures and prevent chronic bronchitis, asthma, vinced that vaccines help in almost two-thirds of bronchiectasis, or even tuberculosis. We believe the infectious bronchitis and asthma cases, and that this can be done and that our studies and cannot yet be sure from a culture of the sputum results will encourage others to adopt the method which cases will benefit and which will not. We of careful investigation of cough of over six do not even claim that many of our "good results" weeks' duration by physical, bacteriologic, and x-ray ex- aminations. Our roentgenograms, a _ few of which have been in- serted as illustrations, de- _ monstrate clearly how cases with lung parenchyma in- volvement can be differ- entiated from those with- out. Pictures 2, 3, 4, and 5 are examples of types which did well under vac- cine therapy. Pictures 6 and 7 are illustrative of Fig. 6.-Asthma wiith cardiac en- Fig. 7.-Infiltration at right hilus does not do well spreading into lung parenchyma. This types whichtyp hdidddntowelnot do well largement.under vaccine.This type type does not improve under vaccine. November, 1929 VACCINE THERAPY-VOORSANGER AND FIRESTONE 339 may not have been just as-good under rest with- tone therapy in England and France, but the results are certainly not as satisfactory or permanent as when out a vaccine. We give our results for what they the specific sensitization is found. are worth, believing firmly that many patients However, I feel there are a moderate number of whose asthma or bronchitis is of the infectious bacterial-sensitive asthmatics, and the writers have variety can be aided by vaccine therapy and thus undoubtedly seen more of these patients than are seen in the usual allergic clinic. Bacterial allergy, in my prevented from becoming hopeless chronic types. experience, is very uncommon in children and young CONCLUSIONS adults. Superimposed sinusitis and bronchitis is not infrequent. The clearing up of sinus infection by sur- In a study of 481 cases of chronic cough of gery at times in nonsensitive patients is necessary, over six weeks' duration we were able to segre- but I agree with Doctor Firestone that vaccine ther- gate sixty-six cases of infectious bronchitis and apy should precede and follow such surgery to build up immunity or produce desensitization. The use of asthma that had received vaccine therapy. In sputum filtrates made according to Wilmer's tech- our sixty-six cases receiving vaccine therapy we. nique has been of value in a few cases in my work, classify 63.6 per cent as well and improved, and and the ust of vaccines in pure cultures which give 36.4 per cent as unimproved. local reactions with intradermal testing is to be rec- ommended. The use of x-ray therapy, as recom- A series of twenty-two cases treated with stock mended by various men, has been given a definite respiratory vaccine give parallel results, so that trial in my clinic without satisfactory results, and we do not claim specificity of autogenous vaccines. there is no justification for it where specific sensitiza- Cultural studies to date do not inform us which tion can be demonstrated. cases will do well; we are influenced by the dura- tion of the illness, age of onset, and history GEORGE PINESS, M. D. (1136 West Sixth Street, Los of repeated colds, influenza, pneumonia, and Angeles).-Since the influenza epidemic of 1918 it has whooping-cough. been our privilege to see a great many cases similar to those described by the essayists today. It is appar- We believe that two-thirds of the cases of in- ently a very common sequela to influenza and other fectious bronchitis and asthma are amenable to acute infectious diseases such as pneumonia, tubercu- vaccine therapy and that failure is the result of losis, and similar conditions. It is very interesting to structural changes in the lung parenchyma or an note, too, that the ages of most of the patients studied by the doctors were in the fourth decade of life al- associated myocardial lesion. though there is a small percentage of very young 490 Post Street. individuals in the first decade of life which is rather REFERENCES unusual in that it is uncommon to see infectious or 1. Voorsanger, William C., and Firestone, Fred: bacterial types of bronchial asthma in young indi- Undiagnosed Cough, Jour. A. M. A., lxxxix, 1137-40, viduals. However, apparently there is an infectious October 1, 1927. history beyond each one of these cases. 2. Walker, I. Chandler: The Treatment of Bron- There are several rather interesting points I wish chial Asthma with Vaccines, Arch. of Internal Medi- to emphasize. The first is that apparently each and cine, xxiii, 220, 1919. every one of these individuals was of a bacterial type 3. Walker, I. Chandler, and Atkinson, June: Bac- because, first, they were tested to proteins of all teriological Examination of Seven Hundred and groups and found nonsensitive; second, the charac- Twenty-Four Sputums from as Many Patients with teristic history of each prior to the onset of the Bacterial Asthma, Arch. of Internal Medicine, iv, present condition; and third, the cases were studied 601-13, April 1928. so thoroughly as to eliminate any possibility of their 4. Cooke, Robert A: Asthma and Preasthmatic being of an allergic type. Conditions, Med. Jour. and Rec., November 4, 1925. I noted with interest the results of treatment with 5. Schloss, 0. M.: Amer. Jour. Diseases of Chil- autogenous and mixed stock respiratory vaccine in dren, iii, 341, 1912. that it was comparative with the results of other 6. Cooke, R. A.: Laryngoscope, xxv, 108, 1915. workers. In our own work we noted that one could 7. Cooke, R. A., and Vander Veer, A., Jr.: Journal obtain equally as good results with the stock respira- of Immunology, i, 201, 1916. tory vaccine as with the autogenous. 8. Rackemann, Francis M., and Graham, Lillian B.: The results of treatment of these cases are interest- The Vaccine Treatment of Asthma, Journal of Im- ing, and the percentage of results is greater than seen munology, viii, No. 4, July 1923. in the average clinic. We are not in accord with the writers that at least 70 per cent oA,,te cases of infec- DISCUSSION tious bronchitis and asthma are v-flnable to vaccine ALBERT H. ROWE, M. D. (242 Moss Avenue, Oak- therapy, but do agree with them that the failures land).-The paper of Doctors Voorsanger and Fire- are the result of subsequent changes in the lung stone is of great interest. It serves to emphasize two parenchyma. things: First, that bacterial allergy exists in a certain I do not agree with Doctor Rowe in his discussion number of cases of asthma. Second, that nonspecific that there are, perhaps, in among this group a number protein therapy by the use of vaccines produces in of food allergy individuals, as the histories are so some asthmatics a nonspecific desensitization. clear-cut and the symptoms so definite and the find- I feel that certain cases in their series probably are ings so typical of a nonallergic infectious bronchitis sensitive to some antigens which have not been dem- and bronchial asthma. onstrated by the writers. During the last two years I have emphasized in several articles the fact that DOCTOR VOORSANGER (Closing).-Answering Doctor food allergy exists in at least 50 per cent of all food- Rowe, we wish to state that our present study deals sensitive patients without skin reactions. Alexander, with bacterial-sensitive asthmatics and does not men- using the intradermal test, is of the same opinion. A tion the large group sensitive to proteins and foods. smaller percentage of pollen- and animal-emanation- We grant the existence of food allergy, but are not sensitive patients have negative skin reactions, and discussing it in this paper; in fact we thought our with these facts in mind and an emphasis on the procedure, which was most careful and painstaking, clinical history, and the use of my elimination diets excluded this group. and environmental control for diagnosis, I have found Doctor Piness has very clearly stressed our main that many cases formerly classified as nonsensitive point, that in most of our cases there is a previous and probably due to bacterial allergy have food or infectious history. He states, however, that he is not other types of specific sensitization. Such cases are "in accord with the writers, that at least 70 per cent helped by nonspecific treatment, as witnessed by pep- of the cases of infectious bronchitis and asthma are 340 CALIFORNIA AND WESTERN MEDICINE Vol. XXXI, No. 5 amenable to vaccine therapy, etc." Our statement "By principle a constitutional Tory, but my man- gave 22.7 per cent as well and 40.9 per cent as im- ners, I should think, would lead most persons to proved, a total of 63.6 per cent, which we feel are amenable to a vaccine. This means that the larger regard me a republican." number, although improved, still have symptoms. Wells early entered the Royal Society, but even In the main we must all agree that the careful the sponsorship of Pitcairn and Baillie was in- observation of asthmatic and bronchitic symptoms adequate to make him a Fellow of the Royal Col- following any acute infection is important to prevent, if possible, changes in the lung parenchyma. If we lege of Physicians. The college banned any who can treat these patients early, before such changes had ever worked as apothecaries, general practi- take place, we may do much toward preventing tioners, or accoucheurs, and was sadly political chronic pulmonary disease. in its organization. Wells protested against its abuses in a letter to Lord Kenyon, and later, when Baillie again urged him to accept a Fellow- THE LURE OFMEDICALHISTORY ship, he declined. The college, founded in 1518, required its fellows to be "profound, sad, dis- WILLIAM CIIARLES WELLS creet, groundedly learned, and deeply studied in physic." Wells had all the qualifications except By WILLIAM DOCK, M. D. the third. San Francisco Wells' most widely known work, and one which was reprinted often and included in many medi- THE men who contributed to the rapid ad- cal texts, was his "Essay on Dew," which was vance of science in the late seventeenth and awarded the Rumford medal. From observations early eighteenth centuries are notable for their made in his own garden with crude instruments, versatility and the broad scope of their interests. he had correctly evaluated the importance of John Hunter, Franklin, Lavoisier, Rumford, and radiation of heat from the objects on which dew Thomas Young, each showed capacity in various condensed, and established the facts of dew for- fields. William Charles Wells was such a searcher mation. His essay was curtly dismissed by for facts, whose studies covered a multitude of Thomas Young in the Quarterly Review, and this subjects, but his cross-grained personality and his added another source of sorrow to the unhappy failure to make known his findings reduced their invalid who had carried out his studies on dew value and eclipsed his worth. in spite of his ill health. His first studies on Wells was born in South Carolina in 1757, but vision were published in 1792, and he continued his parents were Scotch and his education, from his interest in this subject, making important ob- the ages of eleven to fifteen, and eighteen to servations on the optical axis, convergence, pupil- twenty-one, was in Dumfries and Edinburgh. lary changes during accommodation, and on the He spent the three years between these dates effect of belladonna on the pupils and on accom- working for a Charleston physician, and after modation. He described a case of total alopecia, completing his Edinburgh studies stopped a and one of chloasma. In connection with the short time in London, listening to William latter he made some observations on the immu- Hunter, then went as an army surgeon to nity of negroes to certain diseases, and to the Holland, where his quarrels with superiors analogy between the improvement of domestic soon led to his resignation. At Leyden he worked animals by selection and the development of va- on his thesis, De Frigore, and after receiving rieties of man by a similar mechanism of nature. his Edinburgh M.D. he- returned to Charleston What was done for animals artificially "seems to in 1780. His Tory family soon fled to Florida, be done with equal efficiency though more slowly, where he ran the paper, was captain of volun- by nature, in the formation of varieties of man- teers, actor and theatrical manager for the plays kind, fitted for the country which they inhabit. to amuse his fellow refugees. With return of Of the accidental varieties of man, which would peace he went t'TSharleston, only to be jailed for occur among the first scattered inhabitants, some three months in a civil suit, and again he left for one would be better fitted than the others to bear Florida, then Paris, and finally, in 1785, he the diseases of the country. This race would started to practice in London. multiply, while the others would decrease, and as He records that his debts, seven hundred and the darkest would be the best fitted for the fifty dollars when he began practice, increased (African) climate, at length become the most to three thousand dollars in ten years. For prevalent, if not the only race." Darwin regarded several years he scarcely received a fee, but after this observation of Wells' as the "first recognition ten years in practice he was collecting twelve of the principle of natural selection." hundred dollars a year, and was able, gradually, Of the case reports made by Wells those on to pay off all his debts, although his income the infectiousness of erysipelas, on unusual com- never rose over twenty-two hundred dollars. plications of thoracic aneurysm, and one on epi- Through this time his life was austere and his lepsy and hemiplegia due to a traumatic cranial circle of friends, though distinguished, was lim- lesion, and improved by removal of a button of. ited to five men. Of these Matthew Baillie, the bone with a spike projecting into the dura, are greatest physician of the time, was one of the of some interest. His most important medical warmest. In 1812 Wells developed "hydro- contributions concern rheumatic endocarditis and thorax," the condition which we now recognize dropsy. He recorded several cases illustrating the as auricular fibrillation, and from this he suffered relation between rheumatic fever and heart dis- until his death in 1817. He remarked of himself, ease, a fact previously noted by Pitcairn and