Chest
Volume 124, Issue 3, September 2003, Pages 1046-1052
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Clinical Investigations in Critical Care
Exhaled Breath Condensate Nitrite and Its Relation to Tidal Volume in Acute Lung Injury

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Study objective:

Mechanical ventilation may damage the lung. Low tidal volume (Vt) is protective, but Vt is scaled to body weight (BW) and may be high in functionally small ARDS lungs. We hypothesized that exhaled breath condensate (EBC) nitrite (NO2) concentration may increase with lung distension.

Design:

Prospective, noncontrolled study.

Setting:

University hospital and medical ICU.

Patients:

Thirty-five ICU patients requiring mechanical ventilation (severe pneumonia, n = 31; exacerbated COPD, n = 4). Patients were scored according to American and European Consensus Conference on ARDS criteria (AECC) [no lung injury, n = 7; acute lung injury, n = 13; ARDS, n = 15], as well as the Murray lung injury severity score (LISS) [score 0, n = 3; score 0.1 to 2.5, n = 19; score > 2.5, n = 13].

Interventions:

EBC was collected and analyzed for NO2, interleukin (IL)-6, and IL-8. Serum was analyzed for IL-6, IL-8, and procalcitonin.

Results and measurements:

EBC NO2 correlated well with Vt (milliliters per kilogram of BW; r = 0.79, p < 0.0001) and expiratory minute volume (r = 0.60, p < 0.0001) but not with other ventilatory parameters or parameters of pulmonary (EBC IL-6, EBC IL-8) or systemic (serum IL-6, IL-8, and procalcitonin) inflammation. The ratio of EBC NO2 and the size of the Vt correlated directly with lung injury (AECC, r = 0.66, p < 0.0001; LISS, r = 0.84, p < 0.0001).

Conclusion:

EBC NO2 increased linearly with Vt. The ratio of EBC NO2 to Vt is assumed to reflect NO2 release at a given Vt. An increase in this ratio indicates an inappropriate increase of NO2 production most likely due to mechanical stress of the remaining open lung units in injured lungs. We conclude that the EBC NO2/vt ratio may help to identify situations of critical mechanical stress.

Section snippets

Patients

Inclusion criteria for this study were defined by acute respiratory failure due to pneumonia or COPD exacerbation leading to a minimum of 24 h of mechanical ventilation. After that time, patients had to be hemodynamically (no change in IV catecholamines of > 25% of baseline) and respiratory stable (no alteration in ventilator settings). A time frame of an additional 48 h was allowed to reach these criteria and to collect EBC without interference by necessary ICU procedures. Ventilator settings

EBC NO2 and Clinical Scores

EBC NO2 was significantly different in the three patient groups: EBC NO2 was increased in patients with ARDS compared to patients with ALI criteria or patients without signs of lung injury according to both AECC (ARDS, 6.28 ± 1.94 μmol/L; ALI, 4.56 ± 1.32 μmol/L; no lung injury, 3.58 ± 1.52 μmol/L) as well as LISS criteria (ARDS, 6.26 ± 1.71 μmol/L; ALI, 4.61 ± 1.70 μmol/L; no lung injury, 3.23 ± 2.07 μmol/L) [Fig 1].

EBC NO2 and Ventilatory Parameters

Table 2summarizes the correlations between EBC NO2 and ventilatory

Discussion

Nitrite, generated by nitric oxide in aqueous media, has often been regarded to be a marker of inflammation.11,26 It may therefore not have come to anyone's surprise that NO2 was observed in EBC of ventilated patients with lung injury due to pneumonia or exacerbation of COPD. At first sight, a relation of inflammation and EBC NO2 is further suggested by a (weak) correlation of lung injury scores and EBC NO2. However, further analysis of factors influencing EBC NO2 has led us to suggest a

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