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ABSTRACT |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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Airway concentrations of many reactive nitrogen and oxygen species are high in asthma. The stability and bioactivities of these species are pH-dependent; however, the pH of the airway during acute asthma has not previously been studied. As with gastric and urinary acidification, asthmatic airway acidification could be expected dramatically to alter the concentrations and bioactivities/cytotoxicities of endogenous nitrogen oxides. Here, we demonstrate that the pH of deaerated exhaled airway vapor condensate is over two log orders lower in patients with acute asthma (5.23 ± 0.21, n = 22) than in control subjects (7.65 ± 0.20, n = 19, p < 0.001) and normalizes with corticosteroid therapy. Values are highly reproducible, unaffected by salivary or therapeutic artifact, and identical to samples taken directly from the lower airway. Further, at these low pH values, the endogenous airway compound, nitrite, is converted to nitric oxide (NO) in quantities sufficient largely to account for the concentrations of NO in asthmatic expired air, and eosinophils undergo accelerated necrosis. We speculate that airway pH may be an important determinant of expired NO concentration and airway inflammation, and suggest that regulation of airway pH has a previously unsuspected role in asthma pathophysiology. Hunt JF, Fang K, Malik R, Snyder A, Malhotra N, Platts-Mills TAE, Gaston B. Endogenous airway acidification: implications for asthma pathophysiology.
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INTRODUCTION |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Subglottic air is saturated with water that may be condensed
during exhalation (1). In asthma, exhaled airway vapor condensate contains high concentrations of nitrogen oxides (NOx)
and reactive oxygen species, reflecting changes in lower respiratory tract lining fluid during inflammation (2, 3). Of note, the
interactions and toxicity of many of these NOx and reactive oxygen species are critically pH-dependent. We hypothesized
that exhaled airway vapor condensate pH might be low in
asthma, and that this acidification might contribute to asthma
pathophysiology. We report that (1) airway vapor condensate
from patients with acute asthma has a pH substantially lower
than normal; (2) airway acidity appears to be relevant to
asthma in that it both accelerates human eosinophil necrosis
and causes the conversion of endogenous nitrite (NO2
) to nitric oxide (NO); and (3) the acidic airway vapor condensate pH
in asthma normalizes with anti-inflammatory therapy. These observations present asthmatic airway inflammation in an entirely new light, and may have critical diagnostic and therapeutic implications.
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METHODS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Study Subjects
We studied patients with asthma, defined as a history of three or more
episodes of 
2-agonist-reversible airway obstruction, who were admitted to the hospital for dyspnea and demonstrated both tachypnea and
an inspiratory:expiratory ratio less than 0.5. We excluded subjects
who smoked, had clinical evidence of pneumonia, or had a chronic
disease other than asthma. Selected subjects were followed longitudinally with repeated sample collection during and after their hospitalization. Control patients were recruited from hospital staff and inpatients admitted for acute, nonrespiratory diseases. Additionally, three
patients undergoing direct, undiluted tracheal suctioning were studied, and three subjects were studied before and after three consecutive jet nebulization treatments with albuterol (total of 7.5 mg albuterol in 9 ml of normal saline). This study was approved by the
Institutional Human Investigation Committee.
Study Procedure and pH Measurements
Subjects performed quiet tidal breathing through inert one-way valves
and a 0.3-µm particle filter (Marquest Respirgard II, Englewood, CO)
into an aluminum condensing conduit surrounded by coolant. The
conduit had been rinsed with distilled water, dried with forced air, and
frozen at 
40° C. One milliliter of exhaled airway vapor condensate
was obtained during 10 min of breathing. Samples were excluded if
gastric air was expelled during collection. Stable pH was achieved in
all cases after deaeration of the condensate with argon (350 ml/min)
for 10 min. pH was measured using a Cardy Twin pH meter (Horiba,
Japan), or Corning pH microelectrode (Corning, New York).
Eosinophil Studies
Isolation. Fresh human peripheral blood was applied to a density gradient consisting of one part Mono-Poly Resolving Medium (ICN Biomedicals, Aurora, OH), two parts Polymorph (Accurate Science, Westbury, CT), and one part neutrophil isolation media (NIM) (Cardinal, Santa Fe, NM). After centrifugation (25 min; 300 × g; 25° C), the polymorphonuclear (PMN) fraction was washed in Hank's balanced salt solution (HBSS), counted, and incubated with anti-CD16 immunomagnetic microbeads (Milteny Biotech, Sunnyvale, CA) (30 min; 6° C) before being applied to a magnetic column to remove neutrophils (4). An aliquot of eosinophil cell suspension was mixed 1:1 with a 0.4% solution of trypan blue for light microscopic analysis of viability. Eosinophil isolates that were less than 95% pure and viable were discarded.
Determination of apoptosis and necrosis. Mechanism of cell death was assessed by two methods. First, cells underwent Hansel staining and light microscopy for morphologic assessment of apoptosis as evidenced by cytosolic vacuolization, nuclear and cytoplasmic condensation, and presence of apoptotic bodies (5). Additionally, cells underwent DNA quantification using flow cytometry as previously described (6). Briefly, purified eosinophils were fixed in 70% ethanol, pelleted, resuspended in 40 µl of phosphate-citrate buffer for 30 min, washed in HBSS, and stained with propidium iodide (50 µg/ml) for 30 min. Cells were counted by flow cytometry on a FACScan (Immunocytometry Systems, Becton Dickinson, San Jose, CA) for DNA content, gating on forward and side scatter, and (FL-2) area versus FL-2 width to exclude debris. Apoptotic ratios were calculated (ratio of counts in apoptotic range to counts in diploid range).
Chemical Methods
Nitrite was assayed as NO by anaerobic chemiluminescence after reduction in 1% potassium iodide (KI; glacial acetic acid; 50° C) according to the manufacturer's recommendations (NOA 280; Sievers, Boulder, CO). NO evolution from airway vapor condensate was measured
by chemiluminescence in the headspace of 2-ml sealed glass tubes after incubation of 200-µl samples with NO2 (100 µM) (7).
Statistical Analysis
Data are presented as median and range or, when parametrically distributed, as arithmetic or geometric (pH) mean ± SEM. Differences were analyzed by analysis of variance (ANOVA) or ANOVA on ranks with appropriate pairwise comparisons. Linear regression and correlation coefficients were used to assess relationships. Differences were considered significant at p values < 0.05. Statistical calculations were performed using SigmaStat 2.0 (Jandel Corporation, San Rafael, CA).
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RESULTS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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pH
Twenty-two subjects with acute asthma, including 16 subjects treated for less than 48 h with glucocorticoids (mean age 19.5 ± 2.1 yr, 10 males), 19 control subjects (20.5 ± 3.2 yr, 10 males), and 12 subjects with stable asthma (age 21.5 ± 2.0 yr, 6 males) were enrolled. The mean pH of exhaled airway vapor condensate samples from patients with early acute asthma was 5.23 ± 0.21 compared with a mean in the control group of 7.65 ± 0.20 (p < 0.001) (Figure 1). The mean condensate pH of subjects with stable asthma was 7.8 ± 0.1 (p = 0.95 compared with normal subjects). Hospitalized patients who had received systemic glucocorticoid therapy for longer than 48 h had higher condensate pH values than acutely ill subjects, in fact approaching normal (7.4 ± 0.23, n = 11, p < 0.001 versus acute asthmatic subjects on systemic steroids less than 48 h) (Figure 1). Patients followed longitudinally showed steady increases in condensate pH to normal values during anti-inflammatory therapy (Figure 2). Measurements were highly stable and reproducible (average coefficient of variation = 3.3%, 2 to 16 samples each from six normal subjects and three subjects with acute asthma).
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Nonpulmonary causes for airway vapor acidification were
extensively considered. First, direct comparison was made between the pH of condensate and undiluted tracheal secretions
obtained from subjects undergoing subsequent bronchoscopy.
Deaerated condensate pH values were identical to the pH of
unprocessed native lower airway secretions at both low and
normal pH (r2 = 1.0; n = 3). Further, there was no association
between the pH of condensate and matched salivary samples
(n = 20; r2 = 0.17; p = NS) (Figure 3), and the pH decline did
not depend on the presence or absence of supplemental oxygen.
There was no change in condensate pH after administration of
0.083% albuterol (three unit dose treatments of 3.0 ml each) by
nebulizer over 45 min to three subjects (one with stable asthma,
and two healthy control subjects), nor by nebulized unbuffered
solutions at pH of 3.5 (three subjects) and 9.8 (one subject). In
this regard, it should also be noted that airway vapor condensate acidosis in subjects with acute asthma did not appear
to be an artifact of airflow obstruction because 2-agonist therapy and methacholine challenge in asthmatic subjects did not
change the pH of condensates, and because nonasthmatic subjects with chronic obstructive pulmonary disease, cystic fibrosis,
and immotile cilia syndrome
though obstructedconsistently had condensate pH values greater than 7.0 (data not shown).
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NO Production
Consistent with our previous report (2), we found that median
condensate NO2 concentrations in asthmatics were substantially higher than in control subjects. However, this effect was
more evident in specimens from treated asthmatic subjects
with median normal condensate pH values (NO2 = 1.5 µM
[range, 0.45 to 2.74] versus median control values of 0.55 µM
[ranage 0.31 to 2.33]; p < 0.001) than in samples from subjects
with acute asthma whose pH values were less than 7.0 (median, 0.77 µM [range, 0.18 to 4.85]; p = NS compared with
control subjects) (Figure 4A). Lower NO2 values in the acidified samples could be accounted for simply by loss of NO. Indeed, NO was evolved from exogenous NO2 added to acute
asthmatic, but not control, condensates in a pH-dependent fashion (Figure 4B). Because of the small volumes of condensate samples, and the importance of controlling for airflow when measuring NO concentrations from the human lung
(8), we used an in vitro model of airflow through acidified water (pH 5.0) with a physiologically relevant concentration of
NaNO2 (100 µM) (7) to further assess NO evolution from
mildly acidified NO2. This system evolved NO at a rate (2.7 nanomoles/min) adequate fully to account for the high NO
concentrations exhaled by asthmatic patients (9), assuming an
airway lining fluid volume of 25 ml (10) (Figure 4C).
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Eosinophils
Morphologic and nuclear DNA content studies of isolated human eosinophils from two subjects with asthma revealed that
86 ± 4% of cells had necrosed after incubation for 48 h at pH
in the range found in acute asthmatic condensate (pH = 6.2).
On the other hand, when incubated for the same time period
at pH 8.0, minimal necrosis occurred (13.5 ± 4.5%, p < 0.01),
but an additional 26% showed morphologic and DNA content
evidence of apoptosis (Figures 5A and 5B). Incubation of the
cells with 250 µM of S-nitrosoglutamyl-cysteine (CGSNO)a
compound of the endogenous S-nitrosothiol classor the peroxynitrite (OONO) donor SIN-1(250 nM), prevented apoptotic cell death at neutral pH (Figures 5C and 5D).
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DISCUSSION |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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We found that the water derived from the airway was acidified
in patients with acute asthma. The pH was sufficient to cause both NO evolution from endogenous NO2 and necrosis of eosinophils. Further, pH normalized during glucocorticoid treatment. These observations suggest that regulation of airway pH
may have a role in the pathophysiology of acute asthma.
Breath condensates have been studied extensively as tools
to measure airway inflammation. They are noninvasive, simple to perform, highly reproducible, and reflect abnormalities noted in specimens obtained bronchoscopically (11, 12)
and in sputum (13). In this regard, condensate levels of nitrate
(NO3), nitrite (NO2) (2), hydrogen peroxide (H2O2) (3),
and certain cytokines (14) are high in asthma. Because the
concentrations and bioactivities of many of these asthma
markers are critically pH-dependent, we speculated that low
airway pH could contribute substantially to airway inflammation in asthma. Several lines of evidence had suggested a possible role for abnormalities of airway pH in this setting. These
included the observations that (1) citric acid inhalation causes
acute cough and bronchoconstriction in guinea pigs (15); (2)
inhalation of the carbonic anhydrase inhibitor, acetazolamide, protects against cold air- and sulfite-induced bronchoconstriction in asthmatic humans (16, 17). Of note, pH may be generally reduced in human airway inflammation when measured
bronchoscopically (18), though dilution by saliva and/or sampling medium, use of topical anesthetics, reflex responses to
airway instrumentation, and limited sample size have complicated interpretation of direct lower airway studies.
Our evidence suggests that abnormalities in condensate
chemistry reflect intrinsic abnormalities of the airway lining
fluid. Direct comparison revealed that deaerating condensateto control for variations in pH ex vivo with exposure to
atmosphereyielded pH values that were identical to those of
specimens suctioned directly from the tracheobronchial tree.
Although airway pH has not before been studied in acute
asthma, data from our control subjects are consistent with
prior studies of sputum pH (19), and identical to invasive measurement of tracheobronchial secretion pH in 126 patients with
artificial airways (20). We excluded salivary, nasal, and gastric
contamination from our samples as previously described (2),
and showed that there was no association between salivary and
condensate pH. We also demonstrated that condensate acidity
was not likely to have been caused either by airflow obstruction itself or by inhaled asthma medications, as (1) three consecutive albuterol nebulizer treatments caused no change in
pH, and (2) patients admitted for nonasthmatic obstructive pulmonary disease who were treated similarly to patients with asthma had normal condensate pH. Taken together, these observations suggest strongly that acidification of asthmatic airway vapor condensate reflects an intrinsic abnormality in the
regulation of nonvolatile species in the lower airway.
Our data suggest that pH is a determinant of NOx concentrations and bioactivities in the airways of subjects with acute
asthma. In particular, NO2 protonation to form nitrous acid
(HNO2, negative logarithm of the acid ionization constant
[pKa] = 3.4) (21) resulted in evolution of NO gas. Of note, expired NO concentrations are high in asthmatic patients and decrease with glucocorticoid therapy (22). The observations that
(1) pH conditions in the airways of subjects with acute asthma
favor protonation of the high µM concentrations of airway
NO2 (7)liberating NO in quantities consistent with those observed in expired air; (2) endogenous airway fluid acidification
depletes NO2; and (3) pH normalizes with therapy, raise the
possibility that NO2 may serve as an NOx reservoir, converted
to NO by airway acidification during an asthma exacerbation.
From a teleological standpoint, airway acidosis may have
antimicrobial effects mediated through protonation reactions
involving reactive nitrogen and oxygen species. Nitrite acidification has been proposed as a mammalian host defense mechanism (21). The abundant NO2 of the airway is present as
bacteriotoxic HNO2 in relevant quantities only when the pH is
low. Mycobacterium tuberculosis produces a gene product specifically protecting against the 'cidal effects of HNO2 (23).
Some of the toxicity of HNO2 occurs because of its reactive
decomposition to NO, which is known to inhibit mycobacterial growth (24). Additionally, hydrogen peroxide (H2O2),
which is elevated in the condensed breath of asthmatic patients (3), acts synergistically with HNO2 to kill gram-negative
organisms (21). A decline in airway pH would also favor protonation of the relatively stable NO-superoxide reaction product, peroxynitrite (OONO), to peroxynitrous acid (HONOO; pKa = 6.8) (25), an oxidizing and nitrating species
involved in macrophage-mediated Mycoplasma killing (26).
These observations suggest that mild airway acidification may
be a subtle and titratable innate host defense mechanism, one
which takes advantage of the pKa's of weak endogenous acids to defend the airway against airborne pathogens.
Several pathogens also have developed mechanisms to protect against the 'cidal effect of S-nitrosoglutathione (GSNO)
and other S-nitrosothiols (SNO) (27) that are present endogenously in the human airway (28). Though SNO formation and
stability are favored at low pH, SNO concentrations are paradoxically low in the airway of children with near-fatal asthma
(29). We speculate that accelerated catabolism of GSNO in
the asthmatic airwayultimately forming NO and glutathione
may serve as a compensatory mechanism, preserving levels of
anti-oxidant glutathione in the face of the overwhelming nitrosative stress of a fall in airway pH, thus serving as a nitrosative "relief valve." The airway may be viewed as maintaining an intrinsic nitrosative defense system that switches effector molecules from SNOs to HNO2 during acute asthma. We suggest that this switch could be advantageousand might be exploited for therapeutic benefitin subjects infected with an
organism adapted to detoxify SNOs, but not HNO2 (30).
Given the array of cytotoxic reactions associated with mild
acidification, it is not surprising that the pH found in asthmatic condensates caused necrosis of eosinophils in vitro. In this regard, release of mediators from eosinophils is central to
asthma pathophysiology (31), and, in contrast, apoptosis of
these cells is associated with resolution of asthmatic inflammation (32). At normal pH, addition of OONO directly (data
not shown) or from the donor SIN-1 suppressed eosinophil
apoptosissimilar to the effect of the cell-permeable, low
mass endogenous S-nitrosothiol, CGSNO, and other low-molecular-weight NO donors (33). Recent evidence suggests the
possibility that these effects may involve S-nitrosylation reactions, inhibiting proapoptotic proteins such as caspase-3 (34).
On the other hand, incubation of eosinophils at asthmatic pH
induced rapid necrosis. Therefore, we speculate that while
eosinophils are maintained (protected from apoptosis) by high
concentrations of NOx in the baseline asthmatic airwaypermitting low-grade eosinophil-mediated inflammationa sudden drop in airway pH before or during an asthma exacerbation would cause extensive eosinophil necrosis with an acute
release of inflammatory and bronchoconstricting products.
A decline in airway pH may have additional consequences
relevant to asthma. Normal ciliary beating is substantially reduced or eliminated when bronchial epithelium is bathed in
medium with a pH less than 6.5 ex vivo (35), and acidic pH can
increase airway mucous viscosity (36). At pH less than 6.7, epithelial cell membranes are damaged in the tracheal mucosa of
cows, in which the normal tracheal pH is 7.9 (37). Further, exogenous introduction of acids to the airway causes bronchoconstriction, in part through stimulation of ion channels in
capsaicin-sensitive neurons (38)including neurons causing
kinin-induced bronchoconstriction in the guinea pig lung (15,
39). Taken together with evidence for accelerated eosinophil
necrosis and conversion of inert to cytotoxic NOx, these various lines of evidence suggest that there may be a causal relationship between airway acidification and the airflow limitation observed in acute asthma.
In conclusion, we report that airway vapor condensate pH
is over two log orders lower than normal in patients with acute
asthma, with neutralization occurring during systemic anti-
inflammatory therapy. This observation suggests that it may
be critical to consider endogenous pH when interpreting the
airway biochemistry and cell biology of asthma. For example,
we have shown that acidosis at levels seen in subjects with
acute asthma causes both necrosis of human eosinophils and
conversion of airway NO2 to NOeffects relevant to asthma
pathophysiology. Because differences among control, acutely
ill, and treated subjects are robust, and because these simple
assays are noninvasive and reproducible, measurement of pH
may prove clinically useful as a mechanism for diagnosing and
titrating therapy in acute asthma. Further, we speculate that
therapies directed at normalizing airway pH early in the
course of an acute exacerbation of asthma will help to prevent
the cascade of events that leads to airflow obstruction.
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Footnotes |
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Correspondence and requests for reprints should be addressed to Benjamin Gaston, M.D., Department of Pediatrics, Box 386, The University of Virginia Health System, Charlottesville, VA, 22908. E-mail: bmg3g{at}virginia.edu
(Received in original form November 1, 1999 and in revised form December 29, 1999).
Acknowledgments: The authors would like to express our appreciation to Mark Conaway, Ph.D., for his careful review of the manuscript; and to William Ross for his assistance with flow cytometry.
Supported by The Virginia Thoracic Society (J.H.), NIH 1RO1BL59337 (B.G.), American Lung Association Grant RG-110-N (B.G.), NIH Asthma Center Grant 1U19-A134607 (B.G., T.A.E.P.M.), and the University of Virginia Children's Medical Center.
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References |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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1. Baldwin, S. R., R. H. Simon, C. M. Grum, L. H. Ketai, L. A. Boxer, and L. J. Devall. 1986. Oxidant activity in expired breath of patients with adult respiratory distress syndrome. Lancet 1: 11-14 [Medline].
2. Hunt, J., R. E. Byrns, L. J. Ignarro, and B. Gaston. 1995. Condensed expirate nitrite as a home marker for acute asthma [letter]. Lancet 346: 1235-1236 [Medline].
3. Antczak, A., D. Nowak, B. Shariati, M. Krol, G. Piasecka, and Z. Kurmanowska. 1997. Increased hydrogen peroxide and thiobarbituric acid-reactive products in expired breath condensate of asthmatic patients. Eur. Respir. J. 10: 1235-1241 [Abstract].
4. Hansel, T. T., J. D. Pound, D. Pilling, G. D. Kitas, M. Salmon, T. A. Gentle, S. S. Lee, and R. A. Thompson. 1989. Purification of human blood eosinophils by negative selection using immunomagnetic beads. J. Immunol. Methods 122: 97-103 [Medline].
5. Walsh, G. M.. 1997. Mechanisms of human eosinophil survival and apoptosis. Clin. Exp. Allergy 27: 482-487 [Medline].
6. Gong, J., F. Traganos, and Z. Darzynkiewicz. 1994. A selective procedure for DNA extraction from apoptotic cells applicable for gel electrophoresis and flow cytometry. Anal. Biochem. 218: 314-319 [Medline].
7. Govindaraju, K., E. A. Cowley, D. H. Eidelman, and D. K. Lloyd. 1997. Microanalysis of lung airway surface fluid by capillary electrophoresis with conductivity detection. Anal. Chem. 69: 2793-2797 [Medline].
8. Silkoff, P. E., P. A. McClean, A. S. Slutsky, H. G. Furlott, E. Hoffstein, S. Wakita, K. R. Chapman, J. P. Szalai, and N. Zamel. 1997. Marked flow-dependence of exhaled nitric oxide using a new technique to exclude nasal nitric oxide. Am. J. Respir. Crit. Care Med. 155: 260-267 [Abstract].
9.
Lundberg, J. O.,
S. L. Nordvall,
E. Weitzberg,
H. Kollberg, and
K. Alving.
1996.
Exhaled nitric oxide in paediatric asthma and cystic fibrosis.
Arch. Dis. Child.
75:
323-326
10.
Rennard, S. I.,
G. Basset,
D. Lecossier,
K. M. O'Donnell,
P. Pinkston,
P.
G. Martin, and
R. G. Crystal.
1986.
Estimation of volume of epithelial
lining fluid recovered by lavage using urea as marker of dilution.
J.
Appl. Physiol.
60:
532-538
11. Arias-Diaz, J., E. Vara, J. Torres-Melero, C. Garcia, W. Baki, J. A. Ramirez-Armengol, and J. L. Balibrea. 1994. Nitrite/nitrate and cytokine levels in bronchoalveolar lavage fluid of lung cancer patients. Cancer 74: 1546-1551 [Medline].
12. Pheng, L. H., C. Francoeur, and M. Denis. 1995. The involvement of nitric oxide in a mouse model of adult respiratory distress syndrome. Inflammation 19: 599-610 [Medline].
13. Kanazawa, H., S. Shoji, M. Yamada, T. Fujii, T. Kawaguchi, S. Kudoh, K. Hirata, and J. Yoshikawa. 1997. Increased levels of nitric oxide derivatives in induced sputum in patients with asthma. J. Allergy Clin. Immunol. 99: 624-629 [Medline].
14. Becher, G., K. Winsel, E. Beck, G. Neubauer, and E. Stresemann. 1997. [Breath condensate as a method of noninvasive assessment of inflammation mediators from the lower airways]. Pneumologie 51(Suppl. 2): 456-459.
15.
Ricciardolo, F. L. M.,
V. Rado,
L. M. Fabbri,
P. J. Sterk,
G. U. Di Maria, and
P. Geppetti.
1999.
Bronchoconstriction induced by citric acid inhalation in guinea pigs: role of tachykinins, bradykinin, and nitric oxide.
Am. J. Respir. Crit. Care Med.
159:
557-562
16. O'Donnell, W. J., M. Rosenberg, R. W. Niven, J. M. Drazen, and E. Israel. 1992. Acetazolamide and furosemide attenuate asthma induced by hyperventilation of cold, dry air. Am. Rev. Respir. Dis. 146: 1518-1523 [Medline].
17.
O'Connor, B. J.,
C. T. Yeo,
Y. M. Chen-Worsdell,
P. J. Barnes, and
K. F. Chung.
1994.
Effect of acetazolamide and amiloride against sodium
metabisulphite-induced bronchoconstriction in mild asthma.
Thorax
49:
1096-1098
18. Guerrin, F., C. Voisin, V. Macquet, R. A. Robin, and P. Lequien. 1971. Apport de la pH metrie bronchique in situ. Prog. Respir. Res. 6: 372-383 .
19. Adler, K., O. Wooten, W. Philippoff, E. Lerner, and M. J. Dulfano. 1972. Physical properties of sputum: 3. Rheologic variability and intrinsic relationships. Am. Rev. Respir. Dis. 106: 86-96 [Medline].
20. Metheny, N. A., B. J. Stewart, L. Smith, H. Yan, M. Diebold, and R. E. Clouse. 1999. pH and concentration of bilirubin in feeding tube aspirates as predictors of tube placement. Nurs. Res. 48: 189-197 [Medline].
21. Klebanoff, S. J.. 1993. Reactive nitrogen intermediates and antimicrobial activity: role of nitrite. Free Radic. Biol. Med. 14: 351-360 [Medline].
22. Kharitonov, S. A., D. H. Yates, and P. J. Barnes. 1996. Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients. Am. J. Respir. Crit. Care Med. 153: 454-457 [Abstract].
23.
Ehrt, S.,
M. U. Shiloh,
J. Ruan,
M. Choi,
S. Gunzburg,
C. Nathan,
Q. Xie, and
L. W. Riley.
1997.
A novel antioxidant gene from Mycobacterium tuberculosis [published erratum appears in J. Exp. Med. 1998;
187:141].
J. Exp. Med.
186:
1885-1896
24.
Long, R.,
B. Light, and
J. A. Talbot.
1999.
Mycobacteriocidal action of
exogenous nitric oxide.
Antimicrob. Agents Chemother.
43:
403-405
25. Koppenol, W. H., J. J. Moreno, W. A. Pryor, H. Ischiropoulos, and J. S. Beckman. 1992. Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem. Res. Toxicol. 5: 834-842 [Medline].
26.
Hickman-Davis, J.,
J. Gibbs-Erwin,
J. R. Lindsey, and
S. Matalon.
1999.
Surfactant protein A mediates mycoplasmacidal activity of alveolar
macrophages by production of peroxynitrite.
Proc. Natl. Acad. Sci.
U.S.A.
96:
4953-4958
27. De Groote, M. A., T. Testerman, Y. Xu, G. Stauffer, and F. C. Fang. 1996. Homocysteine antagonism of nitric oxide-related cytostasis in Salmonella typhimurium. Science 272: 414-417 [Abstract].
28.
Gaston, B.,
J. Reilly,
J. M. Drazen,
J. Fackler,
P. Ramdev,
D. Arnelle,
M. E. Mullins,
D. J. Sugarbaker,
C. Chee,
D. J. Singel,
J. Loscalzo, and
J. S. Stamler.
1993.
Endogenous nitrogen oxides and bronchodilator
S-nitrosothiols in human airways.
Proc. Natl. Acad. Sci. U.S.A.
90:
10957-10961
29. Gaston, B., S. Sears, J. Woods, J. Hunt, M. Ponaman, T. McMahon, and J. S. Stamler. 1998. Bronchodilator S-nitrosothiol deficiency in asthmatic respiratory failure. Lancet 351: 1317-1319 [Medline].
30. Nathan, C.. 1995. Natural resistance and nitric oxide. Cell 82: 873-876 [Medline].
31. Bousquet, J., P. Chanez, J. Y. Lacoste, G. Barneon, N. Ghavanian, I. Enander, P. Venge, S. Ahlstedt, J. Simony-Lafontaine, P. Godard, and F. Michel. 1990. Eosinophilic inflammation in asthma [see Comments]. N. Engl. J. Med. 323: 1033-1039 [Abstract].
32. Woolley, K. L., P. G. Gibson, K. Carty, A. J. Wilson, S. H. Twaddell, and M. J. Woolley. 1996. Eosinophil apoptosis and the resolution of airway inflammation in asthma. Am. J. Respir. Crit. Care Med. 154: 237-243 [Abstract].
33. Beauvais, F., L. Michel, and L. Dubertret. 1995. The nitric oxide donors, azide and hydroxylamine, inhibit the programmed cell death of cytokine-deprived human eosinophils. FEBS Lett. 361: 229-232 [Medline].
34.
Mannick, J. B.,
A. Hausladen,
L. Liu,
D. T. Hess,
M. Zeng,
Q. X. Miao,
L. S. Kane,
A. J. Gow, and
J. S. Stamler.
1999.
Fas-induced caspase
denitrosylation.
Science
284:
651-654
35. Luk, C. K., and M. J. Dulfano. 1983. Effect of pH, viscosity and ionic-strength changes on ciliary beating frequency of human bronchial explants. Clin. Sci. 64: 449-451 [Medline].
36. Holma, B., and P. O. Hegg. 1989. pH- and protein-dependent buffer capacity and viscosity of respiratory mucus: their interrelationships and influence on health. Sci. Total Environ. 84: 71-82 [Medline].
37. Holma, B., M. Lindegren, and J. M. Andersen. 1977. pH effects on ciliomotility and morphology of respiratory mucosa. Arch. Environ. Health 32: 216-226 [Medline].
38. Bevan, S., and P. Geppetti. 1994. Protons: small stimulants of capsaicin-sensitive sensory nerves. Trends Neurosci. 17: 509-512 [Medline].
39. Lou, Y. P., and J. M. Lundberg. 1992. Inhibition of low pH evoked activation of airway sensory nerves by capsazepine, a novel capsaicin-receptor antagonist. Biochem. Biophys. Res. Commun. 189: 537-544 [Medline].
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|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
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|
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|
|
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|
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|
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|
|
|
|
|
|
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|
|
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|
 |
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 H Marteus, D C Tornberg, E Weitzberg, U Schedin, and K Alving Origin of nitrite and nitrate in nasal and exhaled breath condensate and relation to nitric oxide formation Thorax, March 1, 2005; 60(3): 219 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 C. G. Radu, A. Nijagal, J. McLaughlin, L. Wang, and O. N. Witte Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells PNAS, February 1, 2005; 102(5): 1632 - 1637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J F Hunt Informative complexity of exhaled nitrogen oxide chemistry Thorax, January 1, 2005; 60(1): 2 - 3. [Full Text] [PDF]
|
|
|
|
|
|
J C Ojoo, S A Mulrennan, J A Kastelik, A H Morice, and A E Redington Exhaled breath condensate pH and exhaled nitric oxide in allergic asthma and in cystic fibrosis Thorax, January 1, 2005; 60(1): 22 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K Wells, J Vaughan, T N Pajewski, S Hom, L Ngamtrakulpanit, A Smith, A Nguyen, R Turner, and J Hunt Exhaled breath condensate pH assays are not influenced by oral ammonia Thorax, January 1, 2005; 60(1): 27 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Effros, M. B. Dunning III, J. Biller, and R. Shaker The promise and perils of exhaled breath condensates Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1073 - L1080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
D. Ziora, K. Kaluska, and J. Kozielski An increase in exhaled nitric oxide is not associated with activity in pulmonary sarcoidosis Eur. Respir. J., October 1, 2004; 24(4): 609 - 614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 F. L. M. Ricciardolo, P. J. Sterk, B. Gaston, and G. Folkerts Nitric Oxide in Health and Disease of the Respiratory System Physiol Rev, July 1, 2004; 84(3): 731 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 Z. Zhu, T. Zheng, R. J. Homer, Y.-K. Kim, N. Y. Chen, L. Cohn, Q. Hamid, and J. A. Elias Acidic Mammalian Chitinase in Asthmatic Th2 Inflammation and IL-13 Pathway Activation Science, June 11, 2004; 304(5677): 1678 - 1682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.M. Effros Exhaled breath condensate pH Eur. Respir. J., June 1, 2004; 23(6): 961 - 962. [Full Text] [PDF]
|
|
|
|
|
|
G. E. Carpagnano, P. J. Barnes, J. Francis, N. Wilson, A. Bush, and S. A. Kharitonov Breath Condensate pH in Children With Cystic Fibrosis and Asthma: A New Noninvasive Marker of Airway Inflammation? Chest, June 1, 2004; 125(6): 2005 - 2010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G Adamkiewicz, S Ebelt, M Syring, J Slater, F E Speizer, J Schwartz, H Suh, and D R Gold Association between air pollution exposure and exhaled nitric oxide in an elderly population Thorax, March 1, 2004; 59(3): 204 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
H.-W. Shin, C. M. Rose-Gottron, D. M. Cooper, R. L. Newcomb, and S. C. George Airway diffusing capacity of nitric oxide and steroid therapy in asthma J Appl Physiol, January 1, 2004; 96(1): 65 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 W S Tunnicliffe, R M Harrison, F J Kelly, C Dunster, and J G Ayres The effect of sulphurous air pollutant exposures on symptoms, lung function, exhaled nitric oxide, and nasal epithelial lining fluid antioxidant concentrations in normal and asthmatic adults Occup. Environ. Med., November 1, 2003; 60(11): e15 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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F L M Ricciardolo, M C Timmers, J K Sont, G Folkerts, and P J Sterk Effect of bradykinin on allergen induced increase in exhaled nitric oxide in asthma Thorax, October 1, 2003; 58(10): 840 - 845. [Abstract] [Full Text] [PDF]
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C. Gessner, S. Hammerschmidt, H. Kuhn, T. Lange, L. Engelmann, J. Schauer, and H. Wirtz Exhaled Breath Condensate Nitrite and Its Relation to Tidal Volume in Acute Lung Injury Chest, September 1, 2003; 124(3): 1046 - 1052. [Abstract] [Full Text] [PDF]
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M. Zelenina, A. A. Bondar, S. Zelenin, and A. Aperia Nickel and Extracellular Acidification Inhibit the Water Permeability of Human Aquaporin-3 in Lung Epithelial Cells J. Biol. Chem., August 8, 2003; 278(32): 30037 - 30043. [Abstract] [Full Text] [PDF]
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C. Wijkstrom-Frei, S. El-Chemaly, R. Ali-Rachedi, C. Gerson, M. A. Cobas, R. Forteza, M. Salathe, and G. E. Conner Lactoperoxidase and Human Airway Host Defense Am. J. Respir. Cell Mol. Biol., August 1, 2003; 29(2): 206 - 212. [Abstract] [Full Text] [PDF]
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K. S. van's Gravesande, M. E. Wechsler, H. Grasemann, E. S. Silverman, L. Le, L. J. Palmer, and J. M. Drazen Association of a Missense Mutation in the NOS3 Gene with Exhaled Nitric Oxide Levels Am. J. Respir. Crit. Care Med., July 15, 2003; 168(2): 228 - 231. [Abstract] [Full Text] [PDF]
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E. Baraldi, L. Ghiro, V. Piovan, S. Carraro, G. Ciabattoni, P. J. Barnes, and P. Montuschi Increased Exhaled 8-Isoprostane in Childhood Asthma Chest, July 1, 2003; 124(1): 25 - 31. [Abstract] [Full Text] [PDF]
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L. M. Schachter, J. Dixon, R. J. Pierce, and P. O'Brien Severe Gastroesophageal Reflux Is Associated With Reduced Carbon Monoxide Diffusing Capacity Chest, June 1, 2003; 123(6): 1932 - 1938. [Abstract] [Full Text] [PDF]
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E Baraldi, S Carraro, R Alinovi, A Pesci, L Ghiro, A Bodini, G Piacentini, F Zacchello, and S Zanconato Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations Thorax, June 1, 2003; 58(6): 505 - 509. [Abstract] [Full Text] [PDF]
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S. K. Inglis, S. M. Wilson, and R. E. Olver Secretion of acid and base equivalents by intact distal airways Am J Physiol Lung Cell Mol Physiol, May 1, 2003; 284(5): L855 - L862. [Abstract] [Full Text] [PDF]
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 E Baraldi, L Ghiro, V Piovan, S Carraro, F Zacchello, and S Zanconato Safety and success of exhaled breath condensate collection in asthma Arch. Dis. Child., April 1, 2003; 88(4): 358 - 360. [Abstract] [Full Text] [PDF]
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J. Widdicombe, J. F. Hunt, B. Gaston, K. Kostikas, and S. Loukides "Acidopnea" and the dictionary Am. J. Respir. Crit. Care Med., March 1, 2003; 167(5): 800 - 801. [Full Text]
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M. Corradi, G. Folesani, R. Andreoli, P. Manini, A. Bodini, G. Piacentini, S. Carraro, S. Zanconato, and E. Baraldi Aldehydes and Glutathione in Exhaled Breath Condensate of Children with Asthma Exacerbation Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 395 - 399. [Abstract] [Full Text] [PDF]
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D. McShane, J.C. Davies, M.G. Davies, A. Bush, D.M. Geddes, and E.W.F.W. Alton Airway surface pH in subjects with cystic fibrosis Eur. Respir. J., January 1, 2003; 21(1): 37 - 42. [Abstract] [Full Text] [PDF]
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R. M. Effros, B. M. Gaston, and J. F. Hunt Do low exhaled condensate nh4+ concentrations in asthma reflect reduced pulmonary production? Am. J. Respir. Crit. Care Med., January 1, 2003; 167(1): 91 - 92. [Full Text]
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 K Dua, E Bardan, J Ren, Z Sui, and R Shaker Effect of chronic and acute cigarette smoking on the pharyngoglottal closure reflex Gut, December 1, 2002; 51(6): 771 - 775. [Abstract] [Full Text] [PDF]
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S Tate, G MacGregor, M Davis, J A Innes, and A P Greening Airways in cystic fibrosis are acidified: detection by exhaled breath condensate Thorax, November 1, 2002; 57(11): 926 - 929. [Abstract] [Full Text] [PDF]
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 M. Kollarik and B. J Undem Mechanisms of acid-induced activation of airway afferent nerve fibres in guinea-pig J. Physiol., September 1, 2002; 543(2): 591 - 600. [Abstract] [Full Text] [PDF]
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Members of the Task Force:, E. Baraldi, J.C. de Jongste, B. Gaston, K. Alving, P.J. Barnes, H. Bisgaard, A. Bush, C. Gaultier, H. Grasemann, et al. Measurement of exhaled nitric oxide in children, 2001: E. Baraldi and J.C. de Jongste on behalf of the Task Force Eur. Respir. J., July 1, 2002; 20(1): 223 - 237. [Abstract] [Full Text] [PDF]
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E. Demoncheaux, D. Crowther, A. C. Spivey, T. W. Higenbottam, P. J. Barnes, and S. A. Kharitonov Monitoring reactive nitrogen species in biological milieu: A difficult journey Am. J. Respir. Crit. Care Med., June 15, 2002; 165(12): 1670 - 1671. [Full Text] [PDF]
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B. Gaston and J. F. Hunt How Acidopneic Is My Patient? A New Question in the Pulmonary Laboratory Am. J. Respir. Crit. Care Med., May 15, 2002; 165(10): 1349 - 1350. [Full Text] [PDF]
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K. Kostikas, G. Papatheodorou, K. Ganas, K. Psathakis, P. Panagou, and S. Loukides pH in Expired Breath Condensate of Patients with Inflammatory Airway Diseases Am. J. Respir. Crit. Care Med., May 15, 2002; 165(10): 1364 - 1370. [Abstract] [Full Text] [PDF]
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A. H. Snyder, M. E. McPherson, J. F. Hunt, M. Johnson, J. S. Stamler, and B. Gaston Acute Effects of Aerosolized S-Nitrosoglutathione in Cystic Fibrosis Am. J. Respir. Crit. Care Med., April 1, 2002; 165(7): 922 - 926. [Abstract] [Full Text] [PDF]
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W. Formanek, D. Inci, R.P. Lauener, J.H. Wildhaber, U. Frey, and G.L. Hall Elevated nitrite in breath condensates of children with respiratory disease Eur. Respir. J., March 1, 2002; 19(3): 487 - 491. [Abstract] [Full Text] [PDF]
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R. W. Hyde ""I Don't Know What You Guys Are Measuring But You Sure Are Measuring It!"" . A Fair Criticism of Measurements of Exhaled Condensates? Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 561 - 562. [Full Text] [PDF]
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R. M. EFFROS, K. W. HOAGLAND, M. BOSBOUS, D. CASTILLO, B. FOSS, M. DUNNING, M. GARE, W. LIN, and F. SUN Dilution of Respiratory Solutes in Exhaled Condensates Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 663 - 669. [Abstract] [Full Text] [PDF]
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M. Harbord, M. Novelli, B. Canas, D. Power, C. Davis, J. Godovac-Zimmermann, J. Roes, and A. W. Segal Ym1 Is a Neutrophil Granule Protein That Crystallizes in p47phox-deficient Mice J. Biol. Chem., February 8, 2002; 277(7): 5468 - 5475. [Abstract] [Full Text] [PDF]
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O. W. Griffith Glutaminase and the Control of Airway pH . Yet Another Problem for the Asthmatic Lung? Am. J. Respir. Crit. Care Med., January 1, 2002; 165(1): 1 - 2. [Full Text] [PDF]
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L. M. VAN DEN TOORN, S. E. OVERBEEK, J. C. DE JONGSTE, K. LEMAN, H. C. HOOGSTEDEN, and J.-B. PRINS Airway Inflammation Is Present during Clinical Remission of Atopic Asthma Am. J. Respir. Crit. Care Med., December 1, 2001; 164(11): 2107 - 2113. [Abstract] [Full Text] [PDF]
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