Oral theophylline initially seemed promising in the prophylactic treatment of childhood asthma. When compared with placebo, it significantly increased the mean morning peak expiratory flow rate and reduced the mean number of acute nighttime attacks and doses of bronchodilator used. 37 However, it proved to be less promising when its use over one year was compared with the use of inhaled corticosteroids. Although there was no significant difference between theophylline and inhaled corticosteroids in reduction of asthma symptoms, there was an increased use of short-acting beta 2 agonists and oral corticosteroids in children receiving theophylline. 38 In summary, its use in children cannot be recommended because of the potential for serious side effects, such as cardiac arrhythmias or convulsions, if therapeutic blood levels are exceeded. 39
Methemoglobin: NO is absorbed into the blood where its binds to the ion of the heme protein, subsequently producing nitrosyl-hemoglobin, which is oxidized to methemoglobin with the release of nitrates  . Methemoglobin levels should be measured frequently and kept <%. With standard iNO doses, methemoglobinemia is unusual. In the Neonatal Inhaled Nitric Oxide Study Group (NiNOS) trial, the peak level of methemoglobin was %±%  . Premature infants are at a higher risk of methemoglobin toxicity due to reduced levels of methemoglobin reductase, but at iNO doses of <20 ppm, methemoglobin levels were not elevated   .