Prevalence of Vitamin D Deficiency in Treatment-Naïve Subjects with Chronic Pulmonary Aspergillosis
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Participants
2.2. Study Procedure
2.3. Statistical Analysis
3. Results
4. Discussion
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
- Denning, D.W.; Riniotis, K.; Dobrashian, R.; Sambatakou, H. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: Case series, proposed nomenclature change, and review. Clin. Infect. Dis. 2003, 37 (Suppl. 3), S265–S280. [Google Scholar] [CrossRef]
- Sehgal, I.S.; Dhooria, S.; Muthu, V.; Prasad, K.T.; Agarwal, R. An overview of the available treatments for chronic cavitary pulmonary aspergillosis. Expert Rev. Respir. Med. 2020, 14, 715–727. [Google Scholar] [CrossRef] [PubMed]
- Denning, D.W.; Cadranel, J.; Beigelman-Aubry, C.; Ader, F.; Chakrabarti, A.; Blot, S.; Ullmann, A.J.; Dimopoulos, G.; Lange, C. Chronic pulmonary aspergillosis: Rationale and clinical guidelines for diagnosis and management. Eur. Respir. J. 2016, 47, 45–68. [Google Scholar] [CrossRef]
- Bongomin, F.; Harris, C.; Foden, P.; Kosmidis, C.; Denning, D.W. Innate and Adaptive Immune Defects in Chronic Pulmonary Aspergillosis. J. Fungi 2017, 3, 26. [Google Scholar] [CrossRef]
- Harrison, E.; Singh, A.; Morris, J.; Smith, N.L.; Fraczek, M.G.; Moore, C.B.; Denning, D.W. Mannose-binding lectin genotype and serum levels in patients with chronic and allergic pulmonary aspergillosis. Int. J. Immunogenet. 2012, 39, 224–232. [Google Scholar] [CrossRef] [PubMed]
- Wang, F.; Zhang, C.; Jiang, Y.; Kou, C.; Kong, Q.; Long, N.; Lu, L.; Sang, H. Innate and adaptive immune response to chronic pulmonary infection of hyphae of Aspergillus fumigatus in a new murine model. J. Med. Microbiol. 2017, 66, 1400–1408. [Google Scholar] [CrossRef] [PubMed]
- Hewison, M. An update on vitamin D and human immunity. Clin. Endocrinol. 2012, 76, 315–325. [Google Scholar] [CrossRef]
- Herr, C.; Greulich, T.; Koczulla, R.A.; Meyer, S.; Zakharkina, T.; Branscheidt, M.; Eschmann, R.; Bals, R. The role of vitamin D in pulmonary disease: COPD, asthma, infection, and cancer. Respir. Res. 2011, 12, 31. [Google Scholar] [CrossRef]
- Agarwal, R.; Sehgal, I.S.; Dhooria, S.; Aggarwal, A.N.; Sachdeva, N.; Bhadada, S.K.; Garg, M.; Behera, D.; Chakrabarti, A. Vitamin D levels in asthmatic patients with and without allergic bronchopulmonary aspergillosis. Mycoses 2018, 61, 344–349. [Google Scholar] [CrossRef]
- White, J.H. Vitamin D signaling, infectious diseases, and regulation of innate immunity. Infect. Immun. 2008, 76, 3837–3843. [Google Scholar] [CrossRef]
- Sehgal, I.S.; Dhooria, S.; Choudhary, H.; Aggarwal, A.N.; Garg, M.; Chakrabarti, A.; Agarwal, R. Efficiency of A fumigatus-specific IgG and galactomannan testing in the diagnosis of simple aspergilloma. Mycoses 2019, 62, 1108–1115. [Google Scholar] [CrossRef] [PubMed]
- Sehgal, I.S.; Dhooria, S.; Choudhary, H.; Aggarwal, A.N.; Garg, M.; Chakrabarti, A.; Agarwal, R. Utility of Serum and Bronchoalveolar Lavage Fluid Galactomannan in Diagnosis of Chronic Pulmonary Aspergillosis. J. Clin. Microbiol. 2019, 57. [Google Scholar] [CrossRef] [PubMed]
- Denning, D.W.; Page, I.D.; Chakaya, J.; Jabeen, K.; Jude, C.M.; Cornet, M.; Alastruey-Izquierdo, A.; Bongomin, F.; Bowyer, P.; Chakrabarti, A.; et al. Case Definition of Chronic Pulmonary Aspergillosis in Resource-Constrained Settings. Emerg. Infect. Dis. 2018, 24, e171312. [Google Scholar] [CrossRef] [PubMed]
- Al-Shair, K.; Atherton, G.T.W.; Kennedy, D.; Powell, G.; Denning, D.W.; Caress, A. Validity and reliability of the St. George’s Respiratory Questionnaire in assessing health status in patients with chronic pulmonary aspergillosis. Chest 2013, 144, 623–631. [Google Scholar] [CrossRef] [PubMed]
- Sehgal, I.S.; Choudhary, H.; Dhooria, S.; Aggarwal, A.N.; Garg, M.; Chakrabarti, A.; Agarwal, R. Diagnostic cut-off of Aspergillus fumigatus-specific IgG in the diagnosis of chronic pulmonary aspergillosis. Mycoses 2018, 61, 770–776. [Google Scholar] [CrossRef] [PubMed]
- Agarwal, R.; Aggarwal, A.N.; Sehgal, I.S.; Dhooria, S.; Behera, D.; Chakrabarti, A. Utility of IgE (total and Aspergillus fumigatus specific) in monitoring for response and exacerbations in allergic bronchopulmonary aspergillosis. Mycoses 2016, 59, 1–6. [Google Scholar] [CrossRef]
- Dodamani, M.H.; Muthu, V.; Thakur, R.; Pal, A.; Sehgal, I.S.; Dhooria, S.; Aggarwal, A.N.; Garg, M.; Chakrabarti, A.; Agarwal, R. A randomised trial of vitamin D in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Mycoses 2019, 62, 320–327. [Google Scholar] [CrossRef]
- Ok, M.; Einsele, H.; Loeffler, J. Genetic susceptibility to Aspergillus fumigatus infections. Int. J. Med. Microbiol. 2011, 301, 445–452. [Google Scholar] [CrossRef]
- Sirivoranankul, C.; Martinez, M.; Chen, V.; Clemons, K.V.; Stevens, D.A. Vitamin D and experimental invasive aspergillosis. Med. Mycol. 2014, 52, 847–852. [Google Scholar] [CrossRef][Green Version]
- Hu, S.; Dai, J.; Chen, X. Vitamin D reduces autophagy by regulating NF-κB resistance to Aspergillus fumigatus infection. Gene 2020, 753, 144819. [Google Scholar] [CrossRef]
- Boonstra, A.; Barrat, F.J.; Crain, C.; Heath, V.L.; Savelkoul, H.F.; O’Garra, A. 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J. Immunol. 2001, 167, 4974–4980. [Google Scholar] [CrossRef] [PubMed]
- Prietl, B.; Treiber, G.; Pieber, T.R.; Amrein, K. Vitamin D and immune function. Nutrients 2013, 5, 2502–2521. [Google Scholar] [CrossRef] [PubMed]
- Chishimba, L.; Zhang, W.; Andrew Mochridge, A.M.; Niven, R.M.; Al-Shar, K.; Denning, D. Vitamin D deficiency in asthma patients with allergic bronchopulmonary aspergillosis (ABPA). Eur. Respir. J. 2013, 42, P4178. [Google Scholar]
- Kearns, M.D.; Tangpricha, V. The role of vitamin D in tuberculosis. J. Clin. Transl. Endocrinol. 2014, 1, 167–169. [Google Scholar] [CrossRef] [PubMed]
- Ustianowski, A.; Shaffer, R.; Collin, S.; Wilkinson, R.J.; Davidson, R.N. Prevalence and associations of vitamin D deficiency in foreign-born persons with tuberculosis in London. J. Infect. 2005, 50, 432–437. [Google Scholar] [CrossRef] [PubMed]
- Gupta, R.; Gupta, A. Vitamin D deficiency in India: Prevalence, causalities and interventions. Nutrients 2014, 6, 729–775. [Google Scholar] [CrossRef]
Parameter | CPA (n = 230) | Diseased Controls (n = 28) | Healthy Controls (n = 50) | p-Value |
---|---|---|---|---|
Demographic | ||||
Age, years | 43.9 (42–45.7) | 47 (40.3–53.7) | 41.1 (37.2–45.1) | 0.23 |
Male sex | 117 (50.9) | 19 (67.9) | 29 (58) | 0.19 |
BMI, kg/m2 | 19.6 (19–20.2) | 21.2 (19.4–23) | - | 0.08 |
Clinical findings | ||||
Duration of symptoms, years | 1.9 (1.5–2.4) | 1.2 (0.5–1.8) | 0.26 | |
Cough | 200 (87) | 19 (67.9) | 0.02 | |
Dyspnea | 52 (23.4) | 4 (14.3) | 0.34 | |
Recurrent hemoptysis | 156 (68.1) | 8 (28.6) | <0.0001 | |
Spirometry | ||||
FEV1, liters | 1.78 (1.54–2.03) | 1.38 (1.13–1.63) | - | 0.24 |
FVC, liters | 2.24 (2.11–2.36) | 2.13 (1.86–2.39) | - | 0.54 |
FEV1/FVC ratio | 72.8 (70.6–75.1) | 63.7 (57.8–69.5) | - | 0.006 |
ESR | 31.4 (27.5–35.4) | 33.5 (1.9–65.1) | - | 0.85 |
Quality of life (SGRQ) | ||||
Total score | 22.5 (20.6–24.4) | 16.6 (11.2–22) | - | 0.05 |
Symptom domain | 33.9 (32.1–35.7) | 27.5 (21.9–33.1) | - | 0.03 |
Activity domain | 30.5 (27.7–33.3) | 21.9 (13.7–30) | - | 0.04 |
Impact domain | 14.2 (11.9–16.6) | 9.9 (4.6–15.2) | - | 0.23 |
Immunological findings | ||||
A. fumigatus-specific IgG, mgA/L | 100.3 (92.4–108.3) | 12.8 (10.3–15.4) | - | <0.0001 |
A. fumigatus-specific IgE, kUA/L | 1.5 (0.9–2) | 0.3 (0.1–0.8) | - | 0.12 |
Serum Total IgE levels, IU/mL | 714 (533–897) | 423 (226–619) | - | 0.27 |
Peripheral blood eosinophil count, µL | 259 (230–288) | 207 (140–275) | - | 0.23 |
Serum galactomannan, ODI | 0.77 (0.6–0.95) | 0.39 (0.28–0.51) | - | 0.13 |
BALF galactomannan, ODI | 3.7 (3.1–4.3) | - | - | - |
CT thorax findings | ||||
Presence of cavity on CT thorax | 230 (100) | 12 (42.9) | - | <0.0001 |
Parenchymal fibrosis | 179 (78.2) | 23 (82.1) | - | 0.81 |
CPA (230) | Diseased Controls (n = 28) | Healthy Controls (50) | p–Value | |
---|---|---|---|---|
Vitamin D levels, ng/mL | 19.5 (17.6–21.4) | 18.6 (13.9–23.3) | 15.3 (12.6–17.9) | 0.13 |
Vitamin D status, n (%) | 0.67 | |||
Normal | 36 (15.7) | 5 (17.9) | 4 (8) | |
Vitamin D insufficiency | 44 (19.1) | 6 (21.4) | 11 (22) | |
Vitamin D deficiency | 150 (65.2) | 17 (60.7) | 35 (70) |
Parameter | Vitamin D Deficient (n = 150) | Vitamin D Nondeficient (n = 80) | p-Value |
---|---|---|---|
Demographic | |||
Age, years | 41 (39–43) | 49 (46–52) | <0.0001 |
Male gender | 71 (57.5) | 46 (47.3) | 0.09 |
BMI, kg/m2 | 19.5 (18.8–20.2) | 19.8 (18.9–20.8) | 0.61 |
Clinical findings | |||
Duration of symptoms, years | 1.8 (1.4–2.3) | 2.1 (1.2–3) | 0.55 |
Cough | 129 (86) | 71 (88.8) | 0.68 |
Dyspnea | 36 (24.5) | 16 (21.3) | 0.74 |
Recurrent hemoptysis | 101 (67.3) | 55 (69.8) | 0.77 |
Malaise | 24 (16.1) | 18 (22.5) | 0.28 |
Spirometry | |||
FEV1, liters | 1.85 (1.48–2.22) | 1.66 (1.47–1.86) | 0.49 |
FVC, liters | 2.23 (2.08–2.37) | 2.24 (2.01–2.48) | 0.89 |
Inflammatory markers | |||
ESR | 29.6 (25–34) | 34.9 (27–42.8) | 0.21 |
CRP | 30 (17–43) | 13 (5–21) | 0.09 |
Quality of life (SGRQ) | |||
Total score | 23.6 (21–26) | 20.6 (17.6–23.5) | 0.14 |
Symptom domain | 33.7 (31–36) | 34.2 (31–37.2) | 0.79 |
Activity domain | 32 (28–35.6) | 12.6 (9–16) | 0.18 |
Impact domain | 15 (12–18) | 9.9 (4.6–15.2) | 0.30 |
Immunological findings | |||
A. fumigatus-specific IgG, mgA/L | 101.1 (90.9–111.3) | 98.9 (86.2–111.7) | 0.80 |
A. fumigatus-specific IgE, kUA/L | 1.8 (1.1–2.6) | 0.9 (0.4–1.4) | 0.10 |
Serum Total IgE levels, IU/mL | 819 (568–1070) | 517 (293–741) | 0.12 |
Serum galactomannan, ODI | 0.77 (0.6–0.95) | 0.77 (0.42–1.1) | 0.94 |
BALF galactomannan, ODI | 3.7 (2.9–4.5) | 3.6 (2.6–4.6) | 0.94 |
Microbiology | |||
Aspergillus species | 39 (23.4) | 18 (19.8) | 0.53 |
A. fumigatus | 21 | 14 | - |
A. flavus | 18 | 4 | - |
Underlying etiology for CPA | 0.35 | ||
Tuberculosis | 129 (86) | 65 (81.3) | |
Nontuberculosis | 21 (14) | 15 (18.7) | |
CT thorax findings | |||
Number of cavities | 1.8 (1.7–2) | 1.8 (1.6–2) | 0.70 |
Presence of fungal balls | 93 (62) | 55 (68.8) | 0.39 |
Fungal balls | 0.9 (0.8–1) | 0.82 (0.7–1) | 0.48 |
Category of CPA | 0.82 | ||
Simple aspergilloma | 13 (8.7) | 7 (8.8) | |
CCPA | 112 (74.7) | 63 (78.8) | |
CFPA | 25 (16.7) | 10 (12.5) | |
Severe CPA | 79 (52.7) | 37 (46.3) | 0.41 |
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Sehgal, I.S.; Dhooria, S.; Prasad, K.T.; Muthu, V.; Sachdeva, N.; Bhadada, S.K.; Aggarwal, A.N.; Garg, M.; Chakrabarti, A.; Agarwal, R. Prevalence of Vitamin D Deficiency in Treatment-Naïve Subjects with Chronic Pulmonary Aspergillosis. J. Fungi 2020, 6, 202. https://doi.org/10.3390/jof6040202
Sehgal IS, Dhooria S, Prasad KT, Muthu V, Sachdeva N, Bhadada SK, Aggarwal AN, Garg M, Chakrabarti A, Agarwal R. Prevalence of Vitamin D Deficiency in Treatment-Naïve Subjects with Chronic Pulmonary Aspergillosis. Journal of Fungi. 2020; 6(4):202. https://doi.org/10.3390/jof6040202
Chicago/Turabian StyleSehgal, Inderpaul Singh, Sahajal Dhooria, Kuruswamy Thurai Prasad, Valliappan Muthu, Naresh Sachdeva, Sanjay Kumar Bhadada, Ashutosh Nath Aggarwal, Mandeep Garg, Arunaloke Chakrabarti, and Ritesh Agarwal. 2020. "Prevalence of Vitamin D Deficiency in Treatment-Naïve Subjects with Chronic Pulmonary Aspergillosis" Journal of Fungi 6, no. 4: 202. https://doi.org/10.3390/jof6040202
APA StyleSehgal, I. S., Dhooria, S., Prasad, K. T., Muthu, V., Sachdeva, N., Bhadada, S. K., Aggarwal, A. N., Garg, M., Chakrabarti, A., & Agarwal, R. (2020). Prevalence of Vitamin D Deficiency in Treatment-Naïve Subjects with Chronic Pulmonary Aspergillosis. Journal of Fungi, 6(4), 202. https://doi.org/10.3390/jof6040202