How strong is the association between IPF and lung cancer? An answer from airway's DNA.

Idiopathic pulmonary fibrosis is a chronic progressive disease of lung interstitium of unknown etiology with poor prognosis. In patients with IPF, the incidence of lung cancer is much higher than that in the general population. The identification of noninvasive biomarkers for early diagnosis of IPF is of great relevance in consideration of the management of these patients. Among the noninvasive omic markers, an increasing interest has been directed toward the study of genetic alterations of microsatellites (MAs) in exhaled breath condensate (EBC). The aim of this preliminary study was to investigate the MAs, located in chromosomal regions 8p21.3-q11.1 and 17q11.2-q21, that harbor tumor suppressor genes, in EBC and in the paired whole blood (WB) of IPF patients. Eleven IPF patients were compared with 10 healthy control subjects. All subjects underwent collection of the EBC and WB. The EBC was collected using a condenser. Four microsatellite markers (THRA1, D17S579, D17S250 and D8S137) were used for the analysis of MAs. The EBC-DNA and WB-DNA were amplified by PCR; PCR products were analyzed using the ABI Prism 310 DNA. Microsatellite alterations were found in 58.82 % of EBC-DNA and 12.50 % of WB-DNA in patients with IPF (p < 0.01). None of the healthy subjects exhibited MAs in the studied markers. Our findings suggest that these genetic alterations, studied in EBC, may play an important role in the complex genetic basis of IPF. Since these MAs are frequently detected in cancer, they might explain the higher relative risk of tumorigenesis in this disease.

Study of mitochondrial DNA alteration in the exhaled breath condensate of patients affected by obstructive lung diseases.

Mitochondrial DNA (MtDNA) has been studied as an expression of oxidative stress in asthma, COPD, lung cancer and obstructive sleep apnea, but it has been mainly investigated systemically, although the pathogenetic mechanisms begin in the airways and only later progress to systemic circulation. The aim of this study was to investigate the MtDNA alterations in the exhaled breath condensate (EBC) of patients with asthma, COPD and asthma-COPD overlap syndrome (ACOS). In order to analyze better what happens to mitochondria, both locally and systemically, we compared MtDNA/nDNA in blood and EBC of paired patients. Thirteen (13) COPD patients, 14 asthmatics, 23 ACOS (10 according to Spanish guidelines, 13 in line with GINA guidelines) and 12 healthy subjects were enrolled. Patients underwent clinical and functional diagnostic tests as foreseen by the guidelines. They underwent blood and EBC collection. Content of MtDNA and nuclear DNA (nDNA) was measured in the blood cells and EBC of patients by Real Time PCR. The ratio between MtDNA/nDNA was calculated. For the first time we were able to detect MtDNA/nDNA in the EBC. We found higher exhaled MtDNA/nDNA in COPD, asthmatic and ACOS patients respectively compared to healthy subjects (21.9 ± 4.9 versus 6.51 ± 0.21, p < 0.05; 7.9 ± 2.5 versus 6.51 ± 0.21, p = 0.06; 18.3 ± 3.4 versus 6.51 ± 0.21, p < 0.05). The level of exhaled MtDNA/nDNA was positively correlated with the plasmatic one. The levels of MtDNA/nDNA in the EBC, as expression of oxidative stress, are increased in COPD, asthmatic and ACOS patients compared to healthy subjects. These are preliminary results in a small number of well characterized patients that requires confirmation on a larger population. We support new studies directed toward the analysis of exhaled MtDNA/nDNA as a new exhaled non-invasive marker in other inflammatory/oxidative airways diseases.

Pregnancy with cytochrome oxidase-deficient mitochondrial myopathy.

BACKGROUND: Cytochrome oxidase-deficient mitochondrial myopathies represent a heterogeneous group of muscle disorders. Physical stress can cause life-threatening risks related to rhabdomyolysis or respiratory compromise. CASE: A 21-year-old primigravida with cytochrome C oxidase-deficient mitochondrial myopathy who presented for obstetric care at 8 weeks' gestation complained of muscle fatigue and spasm after exertion. The increased metabolic demands of pregnancy led to worsening pain, muscle fatigue, and ultimately complete immobility. CONCLUSION: Cytochrome oxidase-deficient mitochondrial myopathies are rare but serious complications of pregnancy.