Page 43 - Škrgat, Sabina, ed. 2023. Severe Asthma Forum - Monitoring and Treatable Traits in Severe Asthma. Koper: University of Primorska Press. Severe Asthma Forum, 2
P. 43
le 2. Clinical diagnostic criteria for allergic including lung damage and that »watch and 43
bronchopulmonary mycosis in patients without see« strategy might be not enough.
cystic fibrosis (adapted from 7) aspergillus sensitisation and severe asthma clinical outcomes
Pathophysiological abnormalities
1. Current or previous history of asthma or asthmatic and clinical outcomes related to airway
symptoms fungal allergy
2. Peripheral b lood eosinophilia (≥ 500 cells/mm3) Basic immunology
3. Elevated total serum immunoglobulin E levels (IgE ≥ 417 Fungal sensitisation occurs in about 3–10%
IU/mL) of the general population9 and 7–20% of
asthmatics. The prevalence is higher in pa-
4. Immediate cutaneous hypersensitivity or specific IgE for tients with severe asthma (rates between 35–
filamentous fungi 75%)10. The hallmark of AFAD is exaggerat-
ed T2 immunity causing IgE sensitisation to
5. Presence of precipitins or specific IgG for filamentous fungi filamentous fungi and eosinophilic inflamma-
tion7. Airway epithelium is exposed to prote-
6. Filamentous fungal growth in sputum cultures or bronchial olytic enzymes from fungi following deposi-
lavage fluid tion of the spores/hyphae or smaller particles
on the surface. Those enzymes augment the
7. Presence of fungal hyphae in bronchial mucus plugs permeability of the epithelial layer by digest-
ing the proteins of tight junctions, destroying
8. Central bronchiectasis on computed tomography (CT) the integrity of epithelial cells and by digest-
ing the structural proteins of the basement
9. Presence of mucus plugs in central bronchi, based on CT/ membrane. Selective production of TSLP,
bronchoscopy or mucus plug expectoration history IL-25, and IL-23 by epithelial cells and inhi-
bition of IL-12 production by dendritic cells
10. High attenuation mucus in the bronchi on CT (DCs) may be responsible for the shift toward
Th2 responses11. In the study of Balenga and
Filamentous fungi in 4-6 should be identical. co-workers they have shown that a major A.
Patients that meet 6 or more of these criteria are di- fumigatus allergen, Asp f13, which is a serine
agnosed with ABPM. protease, alkaline protease 1 (Alp1), promotes
airway hyper-responsiveness by infiltrating
Many fungal sensitised individuals with the bronchial submucosa and disrupting air-
severe asthma do not fulfil the criteria for way smooth muscle (ASM) cell-extracellu-
ABPA, so in 2006 the term SAFS was intro- lar matrix (ECM) interactions12. The group
duced. Denning and colleagues thus proposed later demonstrated that Alp1 quantities were
the term severe asthma with fungal sensitisa- significantly higher in sputum from patients
tion (SAFS) to describe this aspect of trouble- with Af sensitivity than those without, re-
some asthma and used criteria in opposition gardless of clinical severity of the disease. But
to the ABPA criteria by including an IgE of the amount of Alp1 in the lower airways of
1000 IU/L8. However, SAFS includes asth- asthmatics correlated with severity of disease
matics with sensitisation to any fungus. and interestingly with sputum neutrophil, but
not eosinophil counts. They suggested that it
It seems that AFAD therefore represent is proteolytic destruction of lung tissue, which
an open definition of IgE sensitisation to ther- could promote influx of neutrophils into the
motolerant fungi, therefore a treatable trait airway lumen13.
which has to be seen, longitudinally observed
and treated as appropriate. It covers not only
the most severe forms of the disease as SAFS
and ABPA, but also milder forms of airway
disease. It is important to stress that many pa-
tients with clinically significant fungal allergy
do not have severe asthma. Nevertheless, all
patients with IgE sensitisation to thermotoler-
ant fungi in the context of asthma and other
airway disease are at risk of progressive lung
damage, and as such should be monitored
closely irrespective of a diagnosis of ABPM7.
The terminus AFAD reminds a clinician,
that the disease might progress in other forms
bronchopulmonary mycosis in patients without see« strategy might be not enough.
cystic fibrosis (adapted from 7) aspergillus sensitisation and severe asthma clinical outcomes
Pathophysiological abnormalities
1. Current or previous history of asthma or asthmatic and clinical outcomes related to airway
symptoms fungal allergy
2. Peripheral b lood eosinophilia (≥ 500 cells/mm3) Basic immunology
3. Elevated total serum immunoglobulin E levels (IgE ≥ 417 Fungal sensitisation occurs in about 3–10%
IU/mL) of the general population9 and 7–20% of
asthmatics. The prevalence is higher in pa-
4. Immediate cutaneous hypersensitivity or specific IgE for tients with severe asthma (rates between 35–
filamentous fungi 75%)10. The hallmark of AFAD is exaggerat-
ed T2 immunity causing IgE sensitisation to
5. Presence of precipitins or specific IgG for filamentous fungi filamentous fungi and eosinophilic inflamma-
tion7. Airway epithelium is exposed to prote-
6. Filamentous fungal growth in sputum cultures or bronchial olytic enzymes from fungi following deposi-
lavage fluid tion of the spores/hyphae or smaller particles
on the surface. Those enzymes augment the
7. Presence of fungal hyphae in bronchial mucus plugs permeability of the epithelial layer by digest-
ing the proteins of tight junctions, destroying
8. Central bronchiectasis on computed tomography (CT) the integrity of epithelial cells and by digest-
ing the structural proteins of the basement
9. Presence of mucus plugs in central bronchi, based on CT/ membrane. Selective production of TSLP,
bronchoscopy or mucus plug expectoration history IL-25, and IL-23 by epithelial cells and inhi-
bition of IL-12 production by dendritic cells
10. High attenuation mucus in the bronchi on CT (DCs) may be responsible for the shift toward
Th2 responses11. In the study of Balenga and
Filamentous fungi in 4-6 should be identical. co-workers they have shown that a major A.
Patients that meet 6 or more of these criteria are di- fumigatus allergen, Asp f13, which is a serine
agnosed with ABPM. protease, alkaline protease 1 (Alp1), promotes
airway hyper-responsiveness by infiltrating
Many fungal sensitised individuals with the bronchial submucosa and disrupting air-
severe asthma do not fulfil the criteria for way smooth muscle (ASM) cell-extracellu-
ABPA, so in 2006 the term SAFS was intro- lar matrix (ECM) interactions12. The group
duced. Denning and colleagues thus proposed later demonstrated that Alp1 quantities were
the term severe asthma with fungal sensitisa- significantly higher in sputum from patients
tion (SAFS) to describe this aspect of trouble- with Af sensitivity than those without, re-
some asthma and used criteria in opposition gardless of clinical severity of the disease. But
to the ABPA criteria by including an IgE of the amount of Alp1 in the lower airways of
1000 IU/L8. However, SAFS includes asth- asthmatics correlated with severity of disease
matics with sensitisation to any fungus. and interestingly with sputum neutrophil, but
not eosinophil counts. They suggested that it
It seems that AFAD therefore represent is proteolytic destruction of lung tissue, which
an open definition of IgE sensitisation to ther- could promote influx of neutrophils into the
motolerant fungi, therefore a treatable trait airway lumen13.
which has to be seen, longitudinally observed
and treated as appropriate. It covers not only
the most severe forms of the disease as SAFS
and ABPA, but also milder forms of airway
disease. It is important to stress that many pa-
tients with clinically significant fungal allergy
do not have severe asthma. Nevertheless, all
patients with IgE sensitisation to thermotoler-
ant fungi in the context of asthma and other
airway disease are at risk of progressive lung
damage, and as such should be monitored
closely irrespective of a diagnosis of ABPM7.
The terminus AFAD reminds a clinician,
that the disease might progress in other forms
