537
come of treatment in real field conditions; however, in response
to the question, all patients were older than 18; 51070 were males.
All patients were smear positive in both laboratories (with over 70070
3 to 4+ positive). All patients had chest roentgenograms compati-
ble with moderate to far-advanced (old classification terminology)
pulmonary tuberculosis.
Our protocol guidelines recognized the likelihood that many pa-
tients might have received prior treatment and, in accord with real
life conditions, patients were only excluded from the study if they
admitted to having received more than 14 days of treatment within
the 60-day period before beginning the proposed treatment regi-
men. Therefore, there is no doubt many of the patients had been
previously treated; as we noted, a contemporary survey indicated
a much lower prevalenceof resistance (INH 33070, streptomycin 19070)
overall in the Filipino population. Hence, we concluded that the
enrollment system employed - community promoters from the
church - acted as a network to attract and enlist patients who had
failed therapy elsewhere. To the extent that this limited the number
of drug-susceptible cases in our series, it is regrettable, but the ex-
perience clearly demonstrates the need for tuberculosis treatment
programs to be community wide. Moreover, this unanticipated op-
portunity allowed us to demonstrate in a highly quantitative man-
ner the unfavorable impact of multi-drug resistance on the efficacy
of a nominally adequate regimen. It was and should be a salient
aspect of our report. ~ Dis 1991; 144:939-44), we would like to bring a similar study to
The decision to hospitalize the patients for one month was the
choice of our collaborators in the Philippines. It was their judg-
ment that this would expand our observations regarding toler-
ance/toxicity of the multi-drug regimen including administration
of the thrice-weekly higher doses just prior to discharge. Also, it
was their judgment that this would promote better case-holding.
Certainly, as demonstrated in our recent series of patients treated
in Denver with a six-month regimen, one can delete or shorten an
initial hospital phase if the individual's illness does not merit in-
patient care (1).
We were amused that Drs. Fox and Mitchison underlined for em-
phasis "precisely what training the Promoters had ... ". As indi-
cated in the article, the parish priest, upon instructions from Drs.
Manalo and Tan, asked his promoters "to bring subjects with signs
or symptoms of chronic pulmonary disease (cough and sputum
production) to the church were sputum specimens were ob-
tained ... "Those patients with tuberculosis proven by sputum tests
were admitted to initiate therapy; upon discharge they were assigned
to one single promoter who, as noted, was responsible for directly
observing all subsequent medicine doses, for obtaining serial spu-
tum specimens, and for bringing the patient in for professional ob-
servation if they became more ill (either drug toxicity or tuberculosis).
These guidelines constituted the entire training of the promoters,
and that explicitly is a cardinal point of our study; the community
workers did not require a great deal of technical or professional
instruction to perform their roles. Our simple description of poten-
tial tuberculosis patients led to a 12070 yield (207 of 1,765 sputum
smears were positive for acid-fast bacilli) of individuals brought
to the church. The case-holding was phenomenally high; five
dropouts (3070) from the 144enrolled in the treatment, a figure rare-
ly matched in formal trials and a tribute to the commitment and
motivation of dedicated church workers.
What modifications would we recommend in hindsight? Perhaps
coordinating such a program with regular local health facilitieswould
allow integration of more routine, newly diagnosed previously un-
treated, drug-susceptible cases in the community treatment program.
On the other hand, this approach did help identify many patients
who presumably had been living in a contagious state in the com-
munity. However, for these patients, standard regimens (even those
containing rifampin) would not be sufficient. In retrospect, wewould
advocate early identification of those with multi-drug resistant tuber-
culosis for isolation and tailored intensive chemotherapy, lest they
succumb to their tuberculosis or remain as vectors for untreatable
tuberculosis in generations to come. We hope that these responses
help clarify our report for Drs. Fox, Mitchison, and others.
MICHAEL D. ISEMAN, M.D.
Chief
Clinical Mycobacteriology Service
Division of Infectious Diseases
National Jewish Center for
Immunology and Respiratory Medicine
Professor of Medicine
University of Colorado School of Medicine
JOHN A. SBARBARO, M.D., M.P.H.
Professor of Medicine and Preventive Medicine
University of Colorado School of Medicine
Denver, CO
1. Cohn DL, Catlin BJ, Peterson KL, Judson FN, and Sbarbaro JA. A
62-dose, 6-month therapy for pulmonary and extrapulmonary tuberculosis.
A twice-weekly, directly observed, and cost-effective regimen. Ann Intern
Med 1990; 112:407-15.
MRI OF UPPER AIRWAY IN OBSTRUCTIVE SLEEP APNEA
To the Editor:
With reference to the paper by Ryan and colleagues (Am Rev Respir
the attention of the authors. We studied 12 patients with obstruc-
tive sleep apnea (mean apnea-hypopnea index 48.4 ± 27.2 events/
hour) before and after a trial of nasal continuous positive airway
pressure (CPAP). We were unable to show a statistically significant
difference between patients' pharyngeal volumes (using a similar
magnetic resonance imaging (MRI) technique) after they had used
nasal CPAP nightly for 6 weeks. In addition, the patients did not
show a significant improvement in their apnea-hypopnea indices
after using nasal CPAP nightly when they underwent repeat sleep
studies without the mask on.
It is very interesting that the authors of this paper were able to
find a decrease in the amount of edema and an increase in the mini-
mal cross-sectional area. We also believed that nasal CPAP would
increase the size of the pharynx by decreasing edema, and suggest-
ed in our paper that possibly our technique was not sensitive enough
to detect those changes. We feel that it is much more significant,
however, that the patients' 0 bstructive sleep apnea did not improve
despite treatment. This suggests that even though the pharyngeal
aperture may enlarge with treatment, the patient will continue to
obstruct. This enforces the notion that patients with obstructive
sleep apnea need to use nasal CPAP on a nightly basis.
NANCY A. COLWP, M.D.
Assistant Professor
Medical University of South Carolina
Charleston, South Carolina
A. JAY BWCK, M.D., F.C.C.P.
Professor
University of Florida
Gainesville, Florida
1. Collop N, Block A, Hellard D. The effect of nightly nasal CPAP treat-
ment on underlying obstructive sleep apnea and pharyngeal size. Chest 1991;
99:855-60.
From the Authors:
Wethank Drs. Collop and Block for bringing to our attention their
contribution on the effect of nasal continuous positive airway pres-
sure (CPAP) on obstructive sleep apnea (OSA) and pharyngeal size
(1),which was published after the original submission of our article
on magnetic resonance imaging (MRI) of the upper airway in OSA
before and after chronic nasal CPAP therapy (2). In their study,
they used sagittal MRI images to measure pharyngeal cross-sectional
 538
area before and after 6 weeks of nasal CPAP therapy and were un-
able to show a difference in pharyngeal size. We examined both
sagittal and axial images of the upper airway in our patients. We
selected the axial images for our measurements of pharyngeal cross-
sectional area because of the difficulty we encountered in identify-
ing the lateral boundaries of the pharynx on the sagittal images,
and the additional advantage of obtaining the site and dimensions
of the minimum axial pharyngeal cross-sectional area. Using a differ-
ent MRI pulse sequence and a visual grading system, we also exam-
ined upper airway mucosal water content and found that reduc-
tions in water content following chronic nasal CPAP therapy cor-
related with increases in pharyngeal cross-sectional area.
We completely agree that regular nightly use of nasal CPAP is
necessary for optimal treatment of patients with OSA, and it was
never the intent of our article to suggest otherwise. We used MRI
of the upper airway to advance our understanding of the pathogen-
esis of OSA and of the mechanisms of action of nasal CPAP therapy.
C. FRANK RYAN, M.B., M.R.C.P.I., F.R.C.P.(C)
JOHN A. FLEETHAM, M.D., F.R.C.P.(C)
Division of Respiratory Medicine
Department of Medicine
University Hospital (UBC)
Vancouver, B.C., Canada
1. Collop NA, Block Al, Hellard D. The effect of nightly nasal CPAP
treatment on underlying obstructive sleep apnea and pharyngeal size. Chest
1991; 99:855-60.
2. Ryan CF, Lowe AA, Li D, Fleetham lA. Magnetic resonance imaging
of the upper airway in obstructive sleep apnea before and after chronic na-
sal continuous positive airway pressure therapy. Am Rev Respir Dis 1991;
144:939-44.
STABILITY OF TUBERCULIN TESTS
To the Editor:
A recent article by Gordin and colleagues (1)confirms the instabili-
ty of booster responses. One year after testing, 18070 of the initially
positive skin tests reverted to a negative status while 40070 of the
boosted reactions reverted to negative. Gordin and associates con-
test that a reaction of 15 mm or greater can be used as a cutoff
for considering that a followup tuberculin skin test will be positive.
They note that 25070 of the boosted reactions greater than 15 mm
in size were also negative after a lapse of one year.
In our study (2), we concluded that true converters can be detect-
ed only with an increase of at least 12mm in the size of the reaction.
This criteria implicitly accepts that some recently infected individu-
als with smaller increases will escape diagnosis. The tuberculin test
alone is not capable of determining true conversion because of its
inherent variability.
The differences between our study and that of Gordin and as-
sociates are likely due to the different epidemiology of tuberculosis
in Spain and the United States. In Spain the high rate of infection
and reinfection is likely to lead to a lesser reversion of the skin test
reaction. In addition, Gordin and coworkers studied patients under
chronic care with a mean age of 69 years, whereas we performed
our study on the general population with a mean age of 28 years.
Fifty-one percent of the individuals in our study had been previous-
ly vaccinated with bacille Calmette-Guerin (BCG). No rigid criteria
is acceptable for identifying true conversion in individuals previ-
ously vaccinated with BCG. The same statement can be applied
to individuals infected with nontuberculous mycobacteria.
From these arguments we believe that the paper of Gordin and
colleagues does not refute our criteria used to define a true convert-
er, especially in young individuals who would benefit from isonia-
zid prophylaxis. In subjects younger than 20 years of age, a number
of factors, including previous BCG vaccination, contact history and
the nature and size of previous tuberculin reactions, need to be con-
sidered in establishing a diagnosis of true tuberculous infection.
P. DE MARCH-AYUELA, M.D.
Dispensario de las Enfermedades del Torax
"Dr. Luis Saye"; Barcelona, Spain
1. Gordin FM, Perez-Stable El, Reid M, Schecter G, Cosgriff L, Flaherty
D, Hopewell PC. Stability of positive tuberculin tests: are boosted reactions
valid? Am Rev Respir Dis 1991; 144:560-3.
2. De March-Ayuela P. Choosing an appropriate criterion for true or false
conversion in serial tuberculin testing. Am Rev Respir Dis 1990; 141:815-20.
From the Authors:
In response to the letter from Dr. P. de March-Ayuela, it is impor-
tant to restate our methods and conclusion. In our original study
(1), we applied three consecutive PPD skin tests to determine the
ability of a chronic care population to demonstrate a positive reac-
tion to a second (booster) or third skin test, all applied within 21
days as a means of identifying past infection. There was no attempt
in our study to determine the conversion (or new infection) rate
in our population, which we believe was misstated in table 4 of Dr.
Ayuela's article on the appropriate criterion for conversion in serial
tuberculin testing (2). In our most recent study (3), we commented
again on the instability of boosted positive reactions and the possi-
ble clinical significance of these tests in determining past infection,
without reference to conversion (or new infection) rate in our
population.
We agree that the definition of a tuberculin convertor as current-
ly defined by the American Thoracic Society (4) may not accurately
identify all newly infected persons. The definition of convertor as
proposed by Dr. Ayuela may, in fact, be more specific. It is unfor-
tunate that we must rely on the skin tests to identify persons infect-
ed with Mycobacterium tuberculosis; hopefully, more accurate sero-
logic tests will be developed and put the skin test de bate "out of
business."
FRED M. GORDIN, M.D.
Department of Veterans Affairs Medical Center
Washington, D.C.
PHILIP C. HOPEWELL, M.D.
San Francisco General Hospital
University of California, San Francisco
1. Gordin FM, Perez-Stable EF, Flaherty D, et al. Evaluation of a third
sequential tuberculin skin test in a chronic care population. Am Rev Respir
Dis 1988; 137:153-7.
2. De March-Ayuela P. Choosing an appropriate criterion for true or false
conversion in serial tuberculin testing. Am Rev Respir Dis 1990; 141:815-20.
3. Gordin FM, Perez-Stable EF, Reid M, et al. Stability of positive tuber-
culin tests: are boosted reactions valid? Am Rev Respir Dis 1991; 144:560-3.
4. American Thoracic Society. The tuberculin skin test. Am Rev Respir
Dis 1981; 124:356-63.