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Vitamin d deficiency and the lung: disease initiator or disease modifier?

Vitamin D deficiency is a global public health problem and has been associated with an increased incidence and severity of many diseases including diseases of the respiratory system. These associations have largely been demonstrated epidemiologically and have formed the basis of the justification for a large number of clinical supplementation trials with a view to improving disease outcomes. However, the trials that have been completed to date and the ongoing experimental studies that have attempted to demonstrate a mechanistic link between vitamin D deficiency and lung disease have been disappointing.

This observation raises many questions regarding whether vitamin D deficiency is truly associated with disease pathogenesis, is only important in the exacerbation of disease or is simply an indirect biomarker of other disease mechanisms?

In this review, we will briefly summarize our current understanding of the role of vitamin D in these processes with a focus on lung disease.

In Utero Exposure to Second-Hand Smoke Aggravates Adult Responses to Irritants: Adult Ovalbumin.

Second-hand smoke (SHS) exposure in utero exacerbates adult responses to environmental irritants. We tested the hypothesis that effects of in utero SHS exposure on modulating physiological and transcriptome responses in BALB/c mouse lungs following ovalbumin (OVA) challenge, extend well into adulthood; and, that the responses show a sex bias.

We exposed BALB/c mice in utero to SHS or filtered air (AIR), then sensitized and challenged all offspring with OVA from 19-23 weeks of age. At the end of the adult OVA challenge, we evaluated pulmonary function, examined histopathology, analyzed bronchoalveolar lavage fluid (BALF) and assessed gene expression changes in the lung samples. All groups exhibited lung inflammation and inflammatory cell infiltration.

Pulmonary function testing (airway hyperresponsiveness, AHR; breathing frequency, f) and BALF (cell differentials, Th1/Th2 cytokines) assessments showed significantly more pronounced lung responses in the SHS-OVA groups than in AIR-OVA groups (AHR, f; eosinophils, neutrophils; IFN-γ, IL-1b, IL-4, IL-5, IL-10, IL-13, KC/CXCL1, TNF-α), with the majority of responses being more pronounced in males than in females. SHS exposure in utero also significantly altered lung gene expression profiles, primarily of genes associated with inflammatory responses and respiratory diseases, including lung cancer and lung fibrosis. Altered expression profiles of chemokines (Cxcl2, Cxcl5, Ccl8, Ccl24), cytokines (Il1b, Il6, Il13) and acute phase response genes (Saa1, Saa3) were confirmed by qRT-PCR.

In conclusion, in utero exposure to SHS exacerbates adult lung responses to OVA challenge and promotes a pro-asthmatic milieu in adult lungs; further, males are generally more affected by SHS-OVA than females.

Erlotinib in the treatment of advanced squamous cell NSCLC.

Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor. Clinical trials have shown its efficacy in advanced non-small cell lung cancer (NSCLC).

We conducted a large retrospective study based on clinical experience aiming to prove erlotinib's efficacy and safety in patients with advanced-stage squamous cell NSCLC. Totally 375 patients with advanced-stage (IIIB, IV) squamous cell NSCLC were treated with erlotinib. Erlotinib was continued until disease progression or intolerable toxicity.

1 (0.3%) complete response (CR), 28 (7.5%) partial responses (PR) and 198 (52.8%) stable diseases (SD) were achieved. Overall response rate (ORR) and disease control rate (DCR) were 7.8% and 60.5%, respectively. Median progression-free survival (PFS) was 3.0 months and median overall survival (OS) was 7.6 months. PFS of patients with CR/PR, SD and PD were 7.6, 3.9 and 1.0 months, respectively (P<0.001). OS of patients with CR/PR, SD and PD were 13.3, 10.9 and 3.8 months, respectively (P<0.001).

The most common adverse effects were rash and diarrhoea. In conclusion erlotinib is effective and well-tolerated in patients with advanced-stage squamous cell NSCLC. Keywords: squamous cell, NSCLC, erlotinib, targeted treatment, EGFR-TKI.

Effect of nasal anti-inflammatory treatment in chronic obstructive pulmonary disease.

Related Articles

Effect of nasal anti-inflammatory treatment in chronic obstructive pulmonary disease.

Am J Rhinol Allergy. 2013 Jul;27(4):273-7

Authors: Callebaut I, Hox V, Bobic S, Bullens DM, Janssens W, Dupont L, Hellings PW

Abstract
BACKGROUND: Sinonasal inflammation and symptoms are often underdiagnosed in chronic obstructive pulmonary disease (COPD) patients. So far, it is not known to what extent anti-inflammatory nasal treatment may reduce sinonasal symptoms in COPD patients. This study was designed to examine the effects of nasal anti-inflammatory treatment on sinonasal symptoms and cough in COPD patients.
METHODS: Thirty-three COPD patients on stable bronchial therapy (salmeterol/fluticasone propionate 50/500 mg b.i.d. for >6 weeks) were randomized to receive fluticasone furoate (FF) or placebo nasal spray at 110 μg once daily for 12 weeks. Sinonasal symptoms and cough were monitored at baseline, at 6 and12 weeks of treatment, and at 4 weeks after cessation of the treatment using a visual analog scale. Levels of cytokines were measured in nasal secretions.
RESULTS: In contrast to the placebo group (n = 13), FF patients (n = 14) reported less nasal blockage (10.62 ± 4.21 mm versus 36.57 ± 8.01 mm; p = 0.0026), postnasal drip (1.46 ± 0.29 score versus 2.83 ± 0.38 score; p = 0.03), and nasal discharge (0.23 ± 0.12 score versus 1.77 ± 0.43 score; p = 0.01) after 6 weeks of treatment compared with baseline, which was still present at 12 weeks. FF patients reported less cough compared with baseline (25.54 ± 4.46 mm versus 36.79 ± 5.75 mm; p = 0.04), which was not the case in the placebo group (49.58 ± 10.44 mm versus 42.00 ± 8.05 mm; p = 0.38). Nine of 14 patients in the FF group (64%) reported slight to total relief of nasal symptoms, and this subgroup had a significant decrease in IL-8 levels in nasal secretions after 6 weeks of treatment (850.7 ± 207.2 pg/mL versus 1608 ± 696.5 pg/mL; p = 0.03) compared with baseline.
CONCLUSION: Nasal FF treatment in COPD patients significantly reduced sinonasal symptoms, in parallel with reduced IL-8 in nasal secretion levels and cough.

PMID: 23883807 [PubMed - in process]

Impact of pneumonia on hospitalizations due to acute exacerbations of COPD.

Related Articles

Impact of pneumonia on hospitalizations due to acute exacerbations of COPD.

Clin Respir J. 2013 Jul 25;

Authors: Andreassen SL, Liaaen ED, Stenfors N, Henriksen AH

Abstract
BACKGROUND AND AIMS: Pneumonia is often diagnosed among patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aims were to find the proportion of patients with pneumonia among admissions due to AECOPD and whether pneumonia has impact on the length of stay (LOS), usage of non-invasive ventilation (NIV) or the in-hospital mortality.
METHODS: Retrospectively all hospitalizations in 2005 due to AECOPD in the Departments of Internal and Respiratory Medicine in one Swedish and two Norwegian hospitals were analyzed. A total of 1144 admittances (731 patients) were identified from patient administrative systems. Pneumonic AECOPD (pAECOPD) was defined as pneumonic infiltrates on chest x-ray and CRP values ≥ 40 mg/L and non-pneumonic AECOPD (npAECOPD) was defined as no pneumonic infiltrate on x-ray and CRP < 40 at admittance.
RESULTS: In admissions with pAECOPD (n=237) LOS was increased (median 9 days versus 5 days, p<0.001) and usage of NIV more frequent (18.1% versus 12.5%, p=0.04), but no significant increase in in-hospital mortality (3.8% versus 3.6%) was found compared to admissions with npAECOPD. A higher proportion of those with COPD GOLD stage I-II had pAECOPD compared to those with COPD GOLD stage III-IV (28.2% versus 18.7 %, p=0.001).
CONCLUSIONS: In-hospital morbidity, but not mortality was increased among admissions with pAECOPD compared to npAECOPD. This may in part be explained by the extensive treatment with antibiotics and NIV in patients with pAECOPD.

PMID: 23889911 [PubMed - as supplied by publisher]

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