(Chest. 2002;121:1670-1676.)
© 2002
American College of Chest Physicians
Sinobronchial Allergic Mycosis*
The SAM Syndrome
Daniel L. Venarske, MD and
Richard D. deShazo, MD
* From the Division of Allergy and Clinical Immunology, Departments of Medicine and Pediatrics, University of Mississippi Medical Center, Jackson, MS.
Correspondence to: Richard D. deShazo, MD, Division of Allergy and Clinical Immunology, Department of Internal Medicine, 2500 North State St, Jackson, MS 39216
 |
Abstract
|
|---|
We contend that the presence of concomitant allergic fungal sinusitis (AFS) and allergic bronchopulmonary mycosis in the same patient represents an expression of the same process of fungal hypersensitivity in the upper and lower airways. We have termed this process the SAM syndrome, an acronym for sinobronchial allergic mycosis. Diagnostic criteria have been established for the SAM syndrome, and the clinical characteristics of one previously unreported and four previously reported patients have been tabulated. Patients with the SAM syndrome have chronic sinusitis involving multiple sinuses, asthma, immediate cutaneous reactivity to fungal allergens, peripheral eosinophilia, and radiographic evidence of bronchiectasis. Total serum IgE levels are usually elevated as well. A variety of chest radiographic abnormalities may occur, ranging from mass lesions to diffuse pulmonary infiltrates and even normal findings on chest radiographs. Patients present for an evaluation of either sinus or lung disease and, at that time, demonstrate no clinical features that distinguish them from patients with isolated sinus or lung disease. All patients reported to date have had clinical responses to therapy with corticosteroids. We postulate that SAM is underdiagnosed in patients with AFS, a disease recently reported from medical centers in the southeastern and western United States. Moreover, since our patient had a mutation in the cystic fibrosis transmembrane conductor regulator (CFTR) gene, we further hypothesize that CFTR gene mutations may play an important role in the pathogenesis of the SAM syndrome.
Key Words: allergic bronchopulmonary mycosis • allergic fungal sinusitis • aspergillosis
|
Introduction
|
|---|
Allergic fungal sinusitis (AFS) is a noninvasive form of fungal sinusitis that is seen in highly atopic individuals with fungal-specific IgE, intractable sinusitis, and nasal polyposis.1
Chronic bacterial sinusitis results when large accumulations of eosinophil-rich allergic mucin containing sparse fungal elements cause mucous impaction and obstruction of the osteomeatal complex. Mucous plugs may become an expanding mass that is capable of penetrating the cartilaginous walls of the sinuses laterally into the orbits or superiorly or posteriorly into the cerebrum.
Over 100 case reports of AFS have followed a series of five patients reported in an abstract in 19812 and the first published series of seven patients described by Katzenstein et al3
in 1983. Subsequently, the diagnostic criteria for AFS were established, and we and others have reported on the clinical features of patients with the condition.4
5
6
AFS has been suggested to be the upper airway manifestation of a similar process occurring in the lower airways of atopic asthmatic patients, which is now termed allergic bronchopulmonary mycosis (ABPM).7
McCarthy and Pepys8
have reported that 10% of patients with ABPM produce nasal plugs that are similar to the airway casts that are present in the bronchi of patients with ABPM. Safirstein9
has reported that nasal discharge containing airway casts improved when a patient with ABPM was treated with corticosteroids. The hypothesis that AFS and ABPM share immunopathogenic mechanisms is further supported by the observation that the distinctive, eosinophil-rich, laminated, allergic mucin is the substrate for the mucous plugs that are common to both conditions.4
10
An IgE-driven hypersensitivity response to low-level fungal colonization may be the principal operative mechanism, but abnormalities of local immunity or mucus itself could play a role in predisposing an individual to this process.3
In that regard, an association between ABPM and cystic fibrosis (CF) has been reported.11
12
If the mechanisms of AFS and ABPM are similar, it would be likely that individuals with one disease would have the propensity to develop the other and that a number of patients with coexistent disease could be identified. In this study, we provide evidence that this is, in fact, the case.
|
Case Report
|
|---|
A 17-year-old, African-American, male, high school athlete with mild intermittent asthma presented to the University of Mississippi Medical Center for the evaluation of chronic sinusitis. A physical examination demonstrated an edematous nasal mucosa, nasal polyps, and thick mucus. Bilateral wheezes were present on auscultation of the chest. Despite long-term antibiotic therapy and therapy with topical nasal steroids, his symptoms of nasal obstruction and intermittent purulent discharge persisted. A CT scan of the sinuses (Fig 1
) revealed multiple soft-tissue densities causing total obstruction of both nares and opacification of the right frontal, ethmoid, maxillary, and sphenoid sinuses, with occlusion of the osteomeatal complex. Lateral bulging of the lamina papyracea of the right orbit and deviation of the nasal septum across the midline to the left were noted, and there was loss of bony margins of the right maxillary and ethmoid structures, which suggested pressure necrosis of cartilage. Areas of hyperattenuating radiodensity, a finding associated with fungal material within the sinuses, were noted within the sinuses on the right.13
View larger version (101K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1. Coronal CT scan of the maxillary and ethmoid sinuses of our patient. There is total obstruction of both nares and opacification of the right ethmoid and maxillary sinuses. The bony margins of the ethmoid and maxillary sinuses on the left are poorly defined, with a slight bulging of the lamina papyracea component of the medial wall of the right orbit. The nasal septum is displaced to the left. There is mucoperiosteal thickening within the left ethmoid sinuses. Other views showed opacification of the right sphenoid sinus.
|
|
In preparation for endoscopic sinus surgery for probable AFS, a preoperative chest radiograph, the first one ever performed on the patient, was obtained. The radiograph appeared to show a large left-suprahilar mass and a right upper-lobe solitary pulmonary nodule (Fig 2
). A helical CT scan of the chest revealed multiple bilateral pulmonary nodules with an upper lobe predominance and right hilar adenopathy with calcification. In the left lung field, a segmental bronchus demonstrated central saccular bronchiectasis, a radiologic hallmark of ABPM (Fig 3
).15
View larger version (111K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2. Erect posteroanterior chest radiograph of our patient showing diffuse peribronchial cuffing, an apparent left suprahilar mass, and a right upper-lobe solitary pulmonary nodule. The hilar findings, caused by massive mucous plugs, have previously been termed "pseudohilar adenopathy."14
|
|
View larger version (93K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3. A CT scan of the mid-upper lung fields in our patient showing central saccular bronchiectasis of a segmental bronchi on the left (arrow) and two pulmonary nodules on the right.
|
|
A minithoracotomy with an open-lung biopsy of the left upper-lobe mass was performed to confirm the diagnosis. Investigation of frozen sections showed bronchiolar mucous impaction, allergic mucin, and rare hyphae with no evidence of tissue invasion. Functional endoscopic sinus surgery was performed with a right-sided polypectomy, anterior and posterior ethmoidectomy, maxillary antrostomy, and frontal recess dissection. Large quantities of polypoid material with a peanut butter consistency were removed from the sinuses. A microscopic examination of material from the right ethmoid sinus showed allergic mucin with layers of mucus, squamous epithelial cells, eosinophils, and an eosinophil-predominant mixed inflammatory cell infiltrate. There were scant hyphae (Fig 4
). Gomori methenamine-silver staining of the mucin revealed small quantities of degenerated fungal hyphae (Fig 5
). A culture of material from the sinuses grew Chrysosporium species. Cultures of the material from the lung failed to grow any organisms.
View larger version (111K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 4. Hematoxylin-eosin stains of mucoid material from the left upper lobe of our patient showing large quantities of mucin containing dense accumulations of eosinophils and hexagonal Charcot-Leyden crystals. Similar findings were present in material taken from the sinus (original x500).
|
|
View larger version (130K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 5. Gomori methenamine-silver stains of mucoid material from the right ethmoid sinus revealing fungal hyphae within allergic mucin. Similar findings were noted on stains of material from the lung (original x500).
|
|
The patient’s preoperative total WBC count was 5,900 cells/µL with 28% eosinophils. Postoperatively, his total serum IgE count was 6,330 kU/L (Specialty Laboratories; Santa Monica, CA; normal count, 
114 kU/L). The patient underwent skin testing with a battery of 60 inhaled allergens and the skin-prick test was positive for Alternaria, Drechslera, Curvularia, Stemphylium, Aspergillus species, Cladosporium, and a number of tree, grass, and weed allergens. Chrysosporium is not available for allergy skin testing or radioallergosorbent tests (RAST).
Material was obtained and commercial assays were performed to detect 87 of the most common mutations in the CF transmembrane conductance regulator (CFTR) gene. The assay utilizes polymerase chain reaction and dot blot with allele-specific oligonucleotide hybridization (Genzyme Genetics; Framingham, MA). One copy of the D1270N mutation in the CFTR gene was detected. Sweat chloride concentrations, as determined by quantitative pilocarpine iontophoresis on each arm, were 19 and 24 mEq/L, with a normal range of < 40 mEq/L.
Postoperatively, the patient was treated with 0.5 mg/kg prednisone daily for 1 month plus topical nasal steroids by inhalation, montelukast sodium (10 mg/d), and nasal lavages (Water-Pik; Water-Pik Technologies; Newport Beach, CA; with a Grossan adapter; Hydromed, Inc, Sherman Oaks, CA) with a saline solution. He received allergen immunotherapy in a single injection for the fungal allergens from which IgE was detected. The patient also received a second immunotherapy injection containing the tree, grass, and weed allergens for which the skin-prick test was positive.
Postoperatively, the patient has been observed in our clinic. His total IgE levels fell to 5,055 kU/L, 3,675 kU/L, and 2,470 kU/L in subsequent months. After 1 month, therapy with oral corticosteroids was switched to alternate-day administration of prednisone (10 mg every other day). At the present time, the patient continues to do well while receiving these medications, with decreasing total IgE levels. He receives surveillance rhinoscopy every 3 months to assess for the reoccurrence of polyps. Evidence of the airways obstruction that was initially present on pulmonary function testing has resolved. Genetic counseling has been provided by a certified genetic counselor.
|
Materials and Methods
|
|---|
Computer-based literature searches were used to identify all case reports of concomitant AFS and ABPM in the medical literature published in English (MEDLINE; National Library of Medicine; Bethesda, MD). These case reports were carefully reviewed, and the findings were compared to those for our patient.
Stringent diagnostic criteria for ABPM and AFS were used for inclusion of case reports in this study. Diagnostic criteria for AFS, as previously published by us,4
include the following: (1) radiologic evidence of sinusitis of one or more paranasal sinuses; (2) histopathologic identification of fungal elements in eosinophil-rich allergic mucin; (3) the absence of invasive fungal disease; and (4) the absence of diabetes, immunodeficiency, or the use of immunosuppressive drugs. Criteria for the diagnosis of ABPM include the presence of asthma and fungal-specific IgE by skin test or RAST, plus any three of the following: (1) elevated total serum IgE levels; (2) peripheral eosinophilia; (3) current or previous pulmonary infiltrates; or (4) central bronchiectasis.16
|
Results
|
|---|
Eight case reports of patients with concomitant AFS and ABPM were identified in the literature.17
18
19
20
21
22
23
Four of the cases did not meet our diagnostic criteria for AFS and ABPM.21
22
23
A 48-year-old woman reported by Travis et al21
did not meet the criteria for ABPM, although testing of a biopsy specimen from a right upper lobe lung nodule did reveal allergic mucin. The patient had no history of asthma or CF, did not demonstrate the presence of fungal-specific IgE by skin test or RAST, and did not have radiographic evidence of central bronchiectasis.21
A second patient in this same series had no evidence of peripheral eosinophilia or radiographic evidence of bronchiectasis.21
A third patient not included did not meet criteria for the diagnosis of either AFS or ABPM. Silver stains of sinus material were negative for fungi, and there were no pulmonary infiltrates or radiographic evidence of bronchiectasis.22
A recent case reported in the New England Journal of Medicine23
of a patient with chronic sinusitis, pulmonary nodules, and hemoptysis met the criteria for the diagnosis for AFS but did not meet the criteria for ABPM. Specifically, the patient did not have eosinophilia, and there were no skin test results or IgE levels provided. The authors reported that they suspected that the patient had invasive pulmonary aspergillosis.
Four other patients met the diagnostic criteria and were included with our patient to form the five case reports used in our analysis.17
18
19
20
The patients were 17 to 55 years of age, and the group included three men and two women. Presenting complaints varied from purulent nasal discharge and obstruction to chest discomfort with cough and fever (Table 1
).
All five patients had a history of chronic sinusitis, and four of the five had undergone sinus surgery prior to diagnosis. All of the patients had a history of asthma. Chest radiographic findings at the time of diagnosis ranged from normal to diffuse pulmonary infiltrates with or without pleural effusion and a mass lesion. Four of five patients had current or previous pulmonary infiltrates, and all had radiographic evidence of bronchiectasis. Four of five patients had elevated serum IgE levels, and all of the patients had peripheral eosinophilia. All patients experienced clinical responses to corticosteroids at a dose of 0.5 mg/kg/d. No long-term data were presented in any case report. Clinical findings in these five patients were not dissimilar from the four patients who did not meet criteria for inclusion in our study.
|
Discussion
|
|---|
The five convincing case reports of patients with concomitant AFS and ABPM reviewed here clearly demonstrate that these diseases occur together and constitute a syndrome of sinobronchial allergic mycosis (SAM). A classification of sinopulmonary syndromes is presented in Table 2
. Patients with SAM are atopic individuals who have asthma, rhinosinusitis, and high levels of total and fungal-specific IgE. The common histopathologic findings of eosinophilic mucin with layers of cellular debris and scant degenerating hyphae in both the upper and lower airways support the conclusion that these are similar hypersensitivity reactions to fungal elements occurring at different locations in the same airway.
Other data also suggest that the pathogenesis of these diseases is similar. In a review of the histopathologic features of AFS, Kahn et al24
noted the histopathologic similarities between ABPM and AFS. There is evidence for the active contribution of both eosinophil-derived and neutrophil-derived products, including eosinophil major basic protein and neutrophil elastase, like that seen in late-phase cutaneous reactions.25
Their findings support earlier suggestions that ubiquitous fungal spores induce a robust, IgE-mediated inflammatory response that induces the viscous mucous secretions these patients experience. Eosinophil-derived and neutrophil-derived toxic proteins have the capacity to induce tissue destruction leading to the layers of eosinophil and epithelial cellular debris that are component parts of the allergic mucin. The mucin obstructs the airways leading to ongoing infection. Since the presence of only small quantities of fungal hyphae in the airway is necessary to initiate the eosinophilic inflammatory process associated with the disease, obstruction to normal drainage of the airway seen in both asthma and chronic sinusitis could be a common feature predisposing an individual to the development of these conditions.
Most, if not all, patients with AFS and concomitant severe lower airways obstruction could be at risk for the development of ABPM. We suspect that the diagnosis of coexistent disease may sometimes be overlooked since at least 50% of patients with AFS have asthma, which is one of the diagnostic criteria for ABPM.4
Why all atopic individuals who demonstrate fungal-specific IgE do not develop one or both of these diseases is unclear. This could reflect a dose-response relationship between obstruction and disease or a more robust IgE-mediated inflammatory response in those patients who develop this form of fungal hypersensitivity. Most patients with AFS have evidence of a fungal-specific IgE response to multiple fungal allergens, as was the case with our patient.5
In our patient, Chrysosporium, a fungus previously implicated in the pathogenesis of AFS, grew from a culture of surgical material obtained from the sinuses and appeared to be the culprit allergen.26
Mast cell-derived products released in such IgE-mediated reactions include histamine, a mucus secretagogue. Variations in the viscosity of the mucus produced or the induction of nasal polyposis, also contributing to airways obstruction, also could play a role in the process. There is no evidence to suggest that AFS or ABPM results from an underlying immunodeficiency. However, the association between ABPM and CF has been known for some time.27
Some reports11
12
suggest that mutations in the CFTR gene are present in patients with ABPM who may have normal sweat chloride levels and lack many of the typical clinical features of CF. Miller et al11
analyzed the CFTR gene in 11 patients with ABPM and found that 1 patient carried two CF mutations (
F508/R347H) and 5 patients carried one mutation (F508, 4 patients; R117H, 1 patient). In a study by Marchand et al,12
the frequency of CFTR gene mutations was also higher in patients with ABPM than it was either in patients with allergic asthma or in subjects seeking genetic counseling.
The higher than expected frequency of CFTR gene mutations in patients with ABPM stimulated us to investigate this possibility in our patient. Our patient is African-American and had one copy of the D1270N mutation with a normal sweat chloride level. The D1270N mutation, which was first described in the heterozygous state in a patient of English and Italian origin, is a missense mutation located in the second adenosine triphosphate-binding region of the CFTR gene.28
This mutation has been reported previously in three series of patients with congenital bilateral absence of the vas deferens,28
29
30
and in a case report of an elderly man with ABPM as a presenting sign of CF.31
In a review of CF carrier frequencies in populations of African origin, two patients were identified who had symptoms suggestive of CF and were heterozygous for the D1270N mutation.32
A sweat test was not performed in one patient and was negative in the other.
The relationship between CFTR gene mutations and AFS is unknown. The possibility that CFTR gene mutations also may contribute to the development of AFS or put patients with either ABPM or AFS at risk for the development of the SAM syndrome requires further study. An epidemiologic survey found that persons heterozygous for the F508 mutations have a higher prevalence of skin- prick tests positive for Aspergillus fumigatus.33
Additional immunologic alterations that have been associated with CFTR gene mutations include reduced levels of interleukin-10, a potent anti-inflammatory cytokine, in the lungs of patients with CF.34
In summary, we conclude that patients with coexistent AFS and ABPM present with symptoms of either or both diseases and are without clinical features to distinguish those with coexistent disease from those with isolated disease. The clinician should, therefore, routinely consider the diagnosis of SAM in patients who have either AFS or ABPM. Patients with coexistent disease have chronic sinusitis and wheezing, and usually require sinus surgery. They have variable chest radiographic appearances at the initial evaluation, although most have pulmonary infiltrates. Although the response to initial corticosteroid therapy is good, the long-term prognosis to this condition is unclear. The associations among mutations in the CFTR gene, ABPM, AFS, and the SAM syndrome require further study.
ADDENDUM: Since the acceptance of our article, Shah et al35
have reported similar findings in four additional patients.
|
Acknowledgements
|
|---|
The authors thank Drs. Steven Bigler and John Conforti for their helpful review of the histopathologic and radiographic features of this patient, and Doris Miller, Karen Davis, and Dawn Chism for assisting with the preparation of the manuscript.
|
Footnotes
|
|---|
Abbreviations: AFS = allergic fungal sinusitis; ABPM = allergic bronchopulmonary mycosis; CF = cystic fibrosis; CFTR = cystic fibrosis transmembrane conductance regulator; RAST = radioallergosorbent test; SAM = sinobronchial allergic mycosis
Received for publication August 30, 2001.
Accepted for publication November 13, 2001.
|
References
|
|---|
-
deShazo, RD, Chapin, K, Swain, RE (1997) Fungal sinusitis. N Engl J Med 337,254-259[Free Full Text]
-
Millar, JW, Johnston, A, Lamb, D (1981) Allergic aspergillosis of the maxillary sinuses [abstract]. Thorax 36,710
-
Katzenstein, A, Sale, SR, Greenberger, PA (1983) Allergic Aspergillus sinusitis: a newly recognized form of sinusitis. J Allergy Clin Immunol 72,89-93[CrossRef][ISI][Medline]
-
deShazo, RD, Swain, RE (1995) Diagnostic criteria for allergic fungal sinusitis. J Allergy Clin Immunol 96,24-35[CrossRef][ISI][Medline]
-
Schubert, MS, Goetz, DW (1988) Evaluation and treatment of allergic fungal sinusitis: I. Demographics and diagnosis. J Allergy Clin Immunol 102,387-394
-
Bent, JP, III, Kuhn, FA (1994) Diagnosis of allergic fungal sinusitis. Otolaryngol Head Neck Surg 111,580-588[CrossRef][ISI][Medline]
-
Goldstein, MF, Dvorin, DJ, Dunsky, EH, et al (1992) Allergic Rhizomucor sinusitis. J Allergy Clin Immunol 90,394-404[CrossRef][ISI][Medline]
-
McCarthy, DS, Pepys, J (1971) Allergic broncho-pulmonary aspergillosis. Clin Allergy 1,261-286
-
Safirstein, BH (1976) Allergic bronchopulmonary aspergillosis with obstruction of the upper respiratory tract. Chest 70,788-790[Abstract/Free Full Text]
-
Slavin, RG, Bedrossian, CW, Hutcheson, PS, et al (1988) A pathologic study of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 81,718-725[CrossRef][ISI][Medline]
-
Miller, PW, Hamosh, A, Macek, M, et al (1996) Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in allergic bronchopulmonary aspergillosis. Am J Hum Genet 59,45-51[ISI][Medline]
-
Marchand, E, Verellen-Dumoulin, C, Mairesse, M, et al (2001) Frequency of cystic fibrosis transmembrane conductance regulator gene mutations and 5T allele in patients with allergic bronchopulmonary aspergillosis. Chest 119,762-767[Abstract/Free Full Text]
-
Mukherji, SK, Figuero, RE, Ginsberg, LE, et al (1998) Allergic fungal sinusitis: CT findings. Radiology 207,417-422[Abstract/Free Full Text]
-
Gefter, WB, Epstein, DM, Miller, WT (1981) Allergic bronchiopulmonary aspergillosis: less common patterns. Radiology 140,307-312[Abstract/Free Full Text]
-
Thompson, BH, Stanford, W, Galvin, JR, et al (1995) Varied radiographic appearances of pulmonary aspergillosis. Radiographics 15,1273-1284[Abstract]
-
Greenberger, PA (1997) Immunologic aspects of lung diseases and cystic fibrosis. JAMA 278,1924-1937[Abstract]
-
Sher, TH, Schwartz, HJ (1988) Allergic Aspergillus sinusitis with concurrent allergic bronchopulmonary Apsergillus: report of a case. J Allergy Clin Immunol 81,844-846[CrossRef][ISI][Medline]
-
Shah, A, Khan, ZU, Chaturvedi, S, et al (1990) Concomittant allergic Aspergillus sinusits and allergic bronchopulmonary aspergillosis associated with familial occurrence of allergic bronchopulmonary aspergillosis. Ann Allergy 64,507-511[ISI][Medline]
-
Bhagat, R, Shah, A, Jaggi, OP, et al (1993) Concomitant allergic broncho-pulmonary aspergillosis and allergic Aspergillus sinusitis with an operated aspergilloma. J Allergy Clin Immunol 91,1094-1096[CrossRef][ISI][Medline]
-
Shah, A, Bhagat, R, Panchal, N, et al (1993) Allergic bronchopulmonary aspergillosis with middle lobe syndrome and allergic Aspergillus sinusitis. Eur Respir J 6,917-18[Abstract]
-
Travis, WD, Kwon-Chung, KJ, Kleiner, DE, et al (1991) Unusual aspects of bronchopulmonary fungal disease: report of two cases due to Curvularia organisms associated with allergic fungal sinusitis. Hum Pathol 22,1240-1248[CrossRef][ISI][Medline]
-
Schwartz, HJ, Witt, WJ, Sher, TH (1992) Allergic bronchopulmonary aspergillosis and allergic aspergillus sinusitis: case report. Ann Allergy 69,447-448[ISI][Medline]
-
. Massachusetts General Hospital (2001) Case records of the Massachusetts General Hospital (case 24–2001). N Engl J Med 345,443-449[Free Full Text]
-
Khan, DA, Cody, DT, George, TJ, et al (2000) Allergic fungal sinusitis: an immunohistologic analysis. J Allergy Clin Immunol 106,1096-1101[CrossRef][ISI][Medline]
-
Leiferman, KM, Fujisawa, T, Gray, BH, et al (1990) Extracellular deposition of eosinophil and neutrophil granule proteins in the IgE-mediated cutaneous late phase reaction. Lab Invest 62,579-589[ISI][Medline]
-
Scheer, L, Shatz, G (1992) Allergic fungal sinusitis (AFS) due to Chrysosporium species [abstract]. Ann Allergy 68,115
-
Brueton, MJ, Ormerod, LP, Shah, KJ, et al (1980) Allergic bronchopulmonary aspergillosis complicating cystic fibrosis in childhood. Arch Dis Child 55,348-353[Abstract]
-
Anguiano, A, Oates, RD, Amos, JA, et al (1992) Congenital bilateral absence of the vas deferens: a primarily genital form of cystic fibrosis. JAMA 267,1794-1797[Abstract]
-
Chillon, M, Casals, T, Mercier, B, et al (1995) Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med 332,1475-1480[Abstract/Free Full Text]
-
Mercier, B, Verlingue, C, Lissens, W, et al (1995) Is congenital bilateral absence of the vas deferens a primary form of cystic fibrosis? Analyses of the CFTR gene in 67 patients. Am J Hum Genet 56,272-277[ISI][Medline]
-
Vilar, MEB, Najib, NM, Chowdhry, I, et al (2000) Allergic bronchopulmonary aspergillosis as presenting sign of cystic fibrosis in an elderly man. Ann Allergy Asthma Immunol 85,70-73[ISI][Medline]
-
Padoa, C, Goldman, A, Jenkins, T, et al (1999) Cystic fibrosis carrier frequencies in populations of African origin. J Med Genet 36,41-44[Abstract/Free Full Text]
-
Kauffmann, F, Chomel, JC, Kitzis, A, et al (1998) F508 heterozygousity and asthma: EGEA-operative Group. Lancet 352,985-986[ISI][Medline]
-
Bonfield, TL, Panuska, JR, Konstan, MW, et al (1995) Inflammatory cytokines in cystic fibrosis lungs. Am J Respir Crit Care Med 152,2111-2118[Abstract]
-
Shah, A, Panchal, N, Agarwal, AK (2001) Concomitant allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis: a review of an uncommon association. Clin Exp Allergy 31,1896-1905[CrossRef][ISI][Medline]
This article has been cited by other articles:
|
|
|
|
 
S. Grossman and L. C. Grossman
Pathophysiology of Cystic Fibrosis: Implications for Critical Care Nurses
Crit. Care Nurse,
August 1, 2005;
25(4):
46 - 51.
[Full Text]
[PDF]
|
|
|
TOP
Abstract
Introduction
